Pomegranate (Punica granatum) is a tree of the Punicaceae family that is widespread all over the world and has several types and therapeutic uses. The current study aimed to investigate the phytochemical compounds by GC analysis and carried out physical characterization of the pomegranate seed oil and its self-nanoemulsifying system. Then antioxidant, anti-diabetic, and anti-lipase activities were investigated for both.The pomegranate seed oil was extracted, and its self-nanoemulsifying system was then prepared. Phytochemical compounds were analyzed by GC, and physical characterization was established of the pomegranate seed oil and its self-nanoemulsifying system. Then antioxidant, anti-diabetic, and anti-lipase activities were investigated for both.The GC–MS analysis revealed that punicic acid, β-eleosteric acid, catalpic acid, α-eleosteric acid, and oleic acid were the most predominant compounds in pomegranate seed oil. Other active compounds like linoleic acid, palmitic acid, stearic acid, and α-linolenic acid were detected in trace percentages. The self-nanoemulsifying system was prepared using various concentrations of surfactant (Tween 80), co-surfactant (Span 80), and pomegranate seed oil. The selected formulation had a PDI of 0.229 ± 0.09 and a droplet size of 189.44 ± 2.1 nm. The free radical scavenging activity of pomegranate seed oil, the self-emulsifying system, and Trolox was conducted using DPPH. The oil-self-nanoemulsifying system showed potent antioxidant activity compared to Trolox. Also, pomegranate oil inhibited α-amylase with a weak IC50 value of 354.81 ± 2.3 µg/ml. The oil self-nanoemulsifying system showed potent activity compared to acarbose and had a weaker IC50 value (616.59 ± 2.1 µg/ml) and a potent IC50 value (43.65 ± 1.9 µg/ml) compared to orlistat.Pomegranate seed oil self-nanoemulsifying system could be applied in the future for the preparation of possible oral medications for the prevention and treatment of oxidative stress, diabetes, and obesity due to its high activity against free radical, amylase, and lipase enzymes compared to pomegranate seed oil itself and the references used. This study reveals that self-nanoemulsion systems can enhance oil drug formulations by improving pharmacokinetics and pharmacodynamics, acting as drug reservoirs, and facilitating efficient oil release.