Given what is known about the practical and theoretical knowledge of medicine and related field around mid-14th century, not only in Europe but generally in the world, it can said with quite a high degree of certainty that there were no efficient curative for any internal bacterial or viral infection.

It is true that the sources of natural antibiotics existed, but this made little difference as the antibiotics themselves are metabolites produced by certain organisms that need to be processed in a specific way to obtain a active substance that can be used in treatment. Thus, even though penicillin can be extracted from the Penicillium fungi, one needed modern medical and biological knowledge to create an antibiotic, because the consumption of unprocessed mold could have easily led to a mycotoxin poisoning. Last but not least, even if some simple form of benzyl penicilin would have been available, its efficiency would be limited, as it is not an antibiotic of choice in the case of infection with Gram-negative bacteria (including Yersinia pestis).

One of the important factors contributing to a significant virulence of the plague is the ability of the bacterium to suppress the natural body response resulting in the increase of production of phagocytes and antibodies. This means that the high mortality of the condition is in part caused by its ability to 'shut down' the natural response mechanisms, making supportive treatment aimed at strengthening the body not too effective.

As evidenced by e.g. Guy de Chauliac in his Inventarium sive chirurgia magna, first published in 1363, a common treatment was an application of cooked or raw onions to the buboes. This offers an insight into the possible thinking process of the contemporary people, as sliced onions or mashed garlic were common ingredients in wound dressing, attested in European writing as early as 9th century CE, when the Bald's Leechbook, an early medieval treatise of medical procedures is thought to have been written. When applied topically to facilitate wound healing, onions and garlic are very efficient disinfectants, if you don't mind the smell, as they both contain allicin, a powerful antimicrobial phytoncide (allyl isothiocyanate, present in mustard seeds and radishes has similar properties). Few years ago it even made news as in 2015 the scientists at Nottingham University tested an eye salve recipe included in the aforementioned Bald's Leechbook and it proved to be effective against MRSA infection (methicyllin-resistant Staphylococcus aureus). Of course, from medical perspective this is nothing new, as the allicin has been isolated in 1940s and its antimicrobial properties were dicovered shortly after.

But could one simply eat a lot of garlic and onions? Not really. Alliinase, an enzyme that transforms an odorless alliine into allicine is deactivated in strongly acidic environment that also facilitates the decomposition of allicine itself, meaning that these substances are unlikely to leave stomach. Although an experimental clinical trial has shown that allicine might somewhat reduce viral infections, the data are still inconclusive while the difference between raw plant material and modern, highly refined and concentrated garlic extracts has not been addressed.

Now, the usage of onions and garlic on buboes indicates that people in 14th century were aware of the curative properties of such plants, and thus were prone to equate an efficacy of the topical application with a similar efficacy of an internal one. This was based on intuitive if incorrect understanding of curative mechanisms, ancient ideas of the curative properties being tied to the medicines rather than the application method.Thus, as the onions or other sources of antimicrobial substances were efficient in reducing inflammation of an open wounds, its application to the skin covering the buboes (inflamed and swollen lymph nodes) was generally ineffective.

Other recipes were similarly ineffective. One of the commonly recalled ones called for marigold flowers and roasted egg shells diluted with sweetened beer, what could have been quite effective in treating gastric problems and worm infection due to antihelmithic properties of the thiophenes in the petals and pollen of that flower, but it was definitely not effective in case of a bacterial infection. Yet another called for the rosin, pitch (possibly for its observed properties), lily root and human excrement, applied topically on the buboes. Some doctors proposed frequent bathing in water with addition of rosewater and vinegar - again, this could have helped after the buboes burst, either naturally or through surgical intervention. Others proposed to sit close to fire to elicit perspiration that was believed to purge the body of disease or re-balance the humours (possibly through an observation that keeping warn might be useful in treatment or convalescence). And there were, of course, treatments bordering on magical practices, such as holding a living bird (usually a hen, as they were easily available) against buboes, so that they could 'draw out' the disease.

On the other hand, the buboes were sometimes drained with the standard wound dressing procedures being used afterwards. This might have had some effect, as the evacuation of the pus reduced the general bacterial burden , increasing chances of remission (please note that the untreated bubonic plague still has an estimated survival rate of roughly 30-40%). It has been also observed that patients in whom the buboes burst on their own their recovered more often that those who did not experience such natural evacuation of pus. This could have worked especially in the minor forms of the condition that is characterized by the inflammation of lymph nodes in a single location. This method, however, could not have been easily used in case of deeply-located lymph nodes. Of course, if the infection developed to the point of general bacteremia (septic form of plague) there was basically nothing that could have been done.

Those with means to spare could have always considered administration of theriac (until 1st century CE also known as mythridatum), an ancient complex medicine then considered a panaceum. Although the actual recipes varied between times and places, theriac was generally a mixture of various spices, herbs, resins, roots, flowers, animal parts (usually powdered horns) and mineral materials (bitumens or clays). The preparation specified by Andromachos of Crete, personal physician to the Emperor Nero (who also popularized the name theriakon) called form over 80 ingredients, and the subsequent preparations were usually no less complex. This mixture became popular in Western Europe from 11th century onwards, with the medical authorities, such as Avicenna, Averroes, Robert Grosseteste or Bernard de Gordon supported the notion that even if theriac is not a true panaceum, it significantly increases vitality and health. Given the complexity and exotic components, it goes without saying that theriacs were expensive. As one can imagine, they were also more or less useless for treating plague, as even though some of the ingredients express some antibacterial properties (such as cinnamon, ginger or cloves), the actual content of these ingredients and their mechanism of action made them ineffective in treating the condition. Nevertheless, it retained its popularity until 19th century due to improvement of well-being reported by many patients, largely attributed to the analgesic and spasmolytic effects of opium it contained.