Cisplatin, a widely used chemotherapeutic agent, has proven efficacy against various malignancies. However, its clinical utility is hampered by its dose-limiting toxicities, including nephrotoxicity, ototoxicity, neurotoxicity, and myelosuppression. This review aims to provide a comprehensive overview of cisplatin toxicity, encompassing its underlying mechanisms, risk factors, and emerging therapeutic strategies. The mechanisms of cisplatin toxicity are multifactorial and involve oxidative stress, inflammation, DNA damage, and cellular apoptosis. Various risk factors contribute to the interindividual variability in susceptibility to cisplatin toxicity. The risk of developing cisplatin-induced toxicity could be related to pre-existing conditions, including kidney disease, hearing impairment, neuropathy, impaired liver function, and other comorbidities. Additionally, this review highlights the emerging therapeutic strategies that could be applied to minimize cisplatin-induced toxicities and aid in optimizing cisplatin treatment regimens, improving patient outcomes, and enhancing the overall quality of cancer care.