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Melatonin, a hormone secreted by the pineal gland, possesses multiple biological activities such as antitumor, antioxidant, and anti‐ischemia. C‐kit⁺ cardiac progenitor cells (CPCs) have emerged as a promising tool for the treatment of heart diseases. However, the senescence of CPCs due to pathological stimuli leads to the decline of CPCs' functions and regenerative potential. This study was conducted to demonstrate whether melatonin antagonizes the senescence of CPCs in response to oxidative stress. Here, we found that the melatonin treatment markedly inhibited the senescent characteristics of CPCs after exposed to sublethal concentration of H₂O₂, including the increase in senescence‐associated β‐galactosidase (SA‐β‐gal)‐positive CPCs, senescence‐associated heterochromatin loci (SAHF), secretory IL‐6 level, and the upregulation of p53 and p21 proteins. Senescence‐associated proliferation …