This is the first study to investigate the effect of ethanol concentrations on the phenolic content and biological activities of Sripanya Punica granatum peel extract. Various concentrations of ethanol, (20 to 80% v/v), were used in the maceration process. Extracts were investigated for total phenolic content by the Folin–Ciocalteu method, antioxidant activities by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2’-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, and anti-tyrosinase activity by a spectrophotometric method. The chemical composition was investigated using high-performance liquid chromatography. The irritation of the extracts was determined by Hen’s egg test–chorioallantoic membrane assay. The results demonstrated that E60, which was extracted using 60% v/v ethanol, had the highest yield (66.23 ± 0.38% w/w), the highest total phenolic content (490.42 ± 7.20 μg GAE/g), and the highest antioxidant and anti-tyrosinase activities. IC₅₀ values on DPPH^• and ABTS^•+ inhibition were 10.97 ± 0.97 and 6.48 ± 0.06 µg/mL, respectively. The 60% v/v ethanol extract (E60) possessed strong tyrosinase inhibition with an IC₅₀ value of 0.10 ± 0.13 µg/mL, which is more potent than kojic acid. The major constituents were punicalagin (4.05 ± 0.26% w/w) and ellagic acid (0.63 ± 0.04% w/w). E60 was safe for topical application since it did not induce irritation. Therefore, we suggest that E60 is a promising agent for further product development.