<p>Amid growing concerns over synthetic preservatives and the rising demand for clean-label products, developing effective plant-based antioxidants is essential, especially for oils rich in omega-3 fatty acids. These oils, valued for their health benefits, are highly prone to oxidation, which reduces nutritional quality and shelf stability. This study evaluates the antioxidant potential of <i>Ocimum sanctum</i> extract (OSE) in stabilizing polyunsaturated fatty acid (PUFA)-rich Perilla oil (PEO) and a palm olein–Perilla oil blend (BPO). Blending PEO with palm olein improved oxidation stability indices while preserving favorable atherogenic and thrombogenic indices, which are vital nutritionally. OSE supplementation further increased oxidative induction periods by 1.37-fold in PEO and 1.16-fold in BPO. Primary and secondary oxidation was effectively suppressed by OSE under accelerated storage, comparable to the synthetic antioxidant butylated hydroxytoluene (BHT). Total oxidation analysis showed rapid deterioration in the control, while OSE above 500ppm significantly slowed oxidation, with 1500ppm OSE in BPO showing the lowest rate, confirming its antioxidant effect. Phytochemical profiling identified major bioactives including eucalyptol, eugenol, β-pinene, and D-limonene, contributing synergistically to preservation. Conservation of α-linolenic acid, a highly oxidation-sensitive PUFA, was greatest in samples with 1500ppm OSE, showing minimal loss (1.02% to 1.23%). Principal component analysis clustered OSE-added samples with those treated with BHT, confirming similar antioxidant equivalence. Our study establishes novel findings, particularly OSE’s preservative effect in Perilla–palm olein blends, offering strong potential as a natural alternative to synthetic antioxidants and paving the way for shelf-stable, nutritious PUFA-rich oils for the food industry and mindful consumers.</p>