Background: Ototoxicity is a common disabling side effect of platinum-based chemotherapy. This study aimed to systematically assess the evidence on the management of platinum-induced ototoxicity in adult cancer patients. Methods: Three databases were searched up to November 1, 2022. Original studies were included if they reported on a pharmacologic or non-pharmacologic intervention to prevent or treat platinum ototoxicity in adults. The articles’ quality was assessed with two grading scales. Results: Eighteen randomized controlled trials and five quasi-experimental studies with 1673 patients were analyzed. Eleven interventions were identified, nine pharmacological and two non-pharmacological. Six of the interventions (sodium thiosulfate, corticoids, sertraline, statins, multivitamins, and D-methionine) showed mild benefit preventing cisplatin-induced ototoxicity. The data must be carefully analyzed due to the low quality and underreporting of side effects. Conclusions: Current interventions have mild benefits preventing cisplatin-induced ototoxicity in adult cancer patients. High-quality research is required to clarify the significance of these findings.