Vaccines play a crucial role in combating infectious diseases and safeguarding public health, yet they may lead to adverse reactions known as vaccine injuries. The coronavirus disease 2019 (COVID-19) mRNA vaccines significantly protected people from the onset of symptoms and reduced the severity of the illness with high efficacy rates. However, in addition to common systemic side effects, such as fever, headache, generalized fatigue, and lymphadenopathy, the vaccines, though rare, caused anaphylaxis or acute coronary syndrome associated with severe allergic reactions. In COVID-19 vaccine-induced systemic side effects, T lymphocytes are hyperactivated, and the enhanced cellular immunity is likely to be responsible for the pathogenesis, for which immunosuppressive properties of nonsteroidal anti-inflammatory drugs (NSAIDs) were effective. On the other hand, in COVID-19 vaccine-induced anaphylaxis or acute coronary syndrome associated with the vaccination, mast cells are hyperactivated, and the exocytotic release of chemical mediators such as histamine and leukotrienes from the cells was primarily responsible for the pathogenesis. Certain medications, including NSAIDs, statins, antibiotics, and antihypertensive agents, are known to inhibit Kv1.3-channel activity in T lymphocytes and decrease pro-inflammatory cytokine production from the cells. Additionally, newer antihistamines, antibiotics, corticosteroids, and various food components effectively stabilize mast cells. Understanding the pharmacological characteristics of these medications or dietary components, along with the mechanisms underlying COVID-19 vaccine-induced adverse reactions, presents opportunities for developing novel therapeutic strategies by focusing on specific cellular targets.