Sepiella maindroni ink, a flavoring and coloring agent in food, has attracted considerable attention due to its various pharmacological activities. Our previous study showed that the melanin of Sepiella maindroni ink (MSMI) can alleviate oxidative damage and delay aging in D-galactose(D-gal)-induced aging mice. This study aimed to reveal the possible mechanisms of the anti-aging effect of MSMI. In this article, a comprehensive analysis of gas chromatography-mass spectrometry (GC-MS)-based metabolomics and microarray-based transcriptomics revealed that 221 mRNAs were differentially expressed and 46 metabolites were significantly changed in the anti-aging progress of MSMI. Integrated analysis of transcript and metabolic profiles indicated that MSMI mainly altered carbohydrate metabolism, lipid metabolism, and insulin signaling pathway. MSMI achieved anti-aging effects not only by reducing oxidative damage and sorbitol toxicity but also by regulating lipid metabolism, improving insulin sensitivity, and reducing the formation of advanced glycation end products (AGEs). Moreover, our findings firstly demonstrated that MSMI could increase the expression of interferon-induced proteins and might be a potential antiviral compound.