Fruit bio-residues can be interesting for the recovery of bioactive molecules, such as phenolic compounds, tocopherols, vitamins, among others. These compounds can be targeted at the food industry and used for the development of functional foods or as food additives. In some cases, fruit epicarps are converted into by-products with non-commercial value, and generally, these fruit parts have a higher content in bioactive compounds than the fruit pulp. From this perspective, S. odorifera, a Brazilian fruit, has an inedible epicarp that could be explored to obtain biological compounds. Therefore, the aims of this study were to evaluate the chemical composition and the antioxidant, anti-proliferative, anti-inflammatory, and antimicrobial bioactivities of this by-product. S. odorifera epicarp showed a total of four organic acids, four phenolic compounds, highlighting the high concentration of anthocyanins (24 ± 1 mg/g dry weight (dw)) and high content of tocopherols (366 ± 2 mg/100 g dw). The hydroethanolic extract showed considerable antioxidant activity (EC50 values of 48.2 ± 0.5 and 27 ± 1 µg/mL for TBARS and OxHLIA assays, respectively), as also antibacterial and antifungal activities (minimal inhibitory concentrations (MICs) ≤ 2.2 mg/mL). The results obtained in this study suggest that Sicana odorifera epicarp represents a reliable option for the development of novel natural-based colorants with functional/bioactive proprieties.