Coffea arabica sediment, a popular agro-by-product from the coffee juice processing industry, contains many phytochemicals, and it is often discarded as waste. The antioxidant and anti-tyrosinase activities of an ethanol extract and its active fractions obtained from Coffea arabica sediment was studied. Additionally, whiteleg shrimp (Litopenaeus vannamei) was treated with the extract and fractions, and the quality during refrigerated storage was evaluated. The most active fraction (P<0.05) fraction III from the Coffea arabica sediment extract showed a total phenolic content of 116.5 mg gallic acid equivalent/g, an inhibitory concentration of 50% value of 27.3 μg/mL in the 2,2-diphenyl-1-picryl hydrazyl test, an absorbance of 3.7 (at 1.0 μg/mL) in the reducing power assay, and 79.5% inhibition for the tyrosinase inhibition test (at 100 μg/mL). Whiteleg shrimp treated with PD-3 and crude extract (CE) retarded the growth of bacteria and spoilage microorganisms in comparison to the control (P<0.05). Lower values in pH, thiobarbituric acid reactive substances, and total volatile base content were enumerated in samples treated with PD-3 and CE (P<0.05) compared to controls. Loss in freshness, protein content, and melanosis formation declined with CE and PD-3 treatments. Our findings showed that Coffea arabica sediment has antioxidant and antimicrobial properties. Also, it could be a promising treatment in melanosis prevention, and a natural additive for extending the shelf life of whiteleg shrimp during refrigerated storage; thus an alternative to traditional sulfites.