Introduction: Kidney transplantation stands out as the optimal treatment for patients with end-stage kidney disease, provided they meet specific criteria for a secure outcome. With the exception of identical twin donor–recipient pairs, lifelong immunosuppression becomes imperative. Unfortunately, immunosuppressant drugs, particularly calcineurin inhibitors like tacrolimus, bring about adverse effects, including nephrotoxicity, diabetes mellitus, hypertension, infections, malignancy, leukopenia, anemia, thrombocytopenia, mouth ulcers, dyslipidemia, and wound complications. Since achieving tolerance is not feasible, patients are compelled to adhere to lifelong immunosuppressive therapies, often involving calcineurin inhibitors, alongside mycophenolic acid or mTOR inhibitors, with or without steroids. Area covered: Notably, these drugs, especially calcineurin inhibitors, possess narrow therapeutic windows, resulting in numerous drug-related side effects. This review focuses on the prevalent immunosuppressive drug-related side effects encountered in kidney transplant recipients, namely nephrotoxicity, post-transplant diabetes mellitus, leukopenia, anemia, dyslipidemia, mouth ulcers, hypertension, and viral reactivations (cytomegalovirus and BK virus). Additionally, other post-kidney-transplantation drugs such as valganciclovir may also contribute to adverse events such as leukopenia. For each side effect, we propose preventive measures and outline appropriate treatment strategies.