Curcumin has been extensively studied for its medicinal advantages, although its therapeutic use is restricted by an absence of aqueous solubility and bioavailability. Piperine from black pepper is thought to synergistically improve the bioavailability of curcumin. Nevertheless, each curcumin and piperine lack aqueous solubility, requiring extraction by non-eco-friendly solvents and additional nano-encapsulation for in vivo software. Exosome-like nanovesicles (ENVs) are pure extracellular vesicles produced by vegetation that are remoted by inexperienced strategies. ENVs purified from a number of edible vegetation comprise host-plant-derived phytochemicals in soluble kind with enhanced bioavailability. Nevertheless, the mixed isolation of two or extra bio-actives with synergistic results from completely different host vegetation in ENV kind has by no means been tried. Herein, we describe a inexperienced methodology to co-purify each curcumin and piperine by mixed homogenization of plant supplies adopted by polyethylene glycol-based precipitation of ENVs from the aqueous extract. ENVs remoted from a combined homogenate of turmeric and pepper (TPENV) possessed each curcumin and piperine. TPENVs confirmed spontaneous intracellular entry and displayed anti-inflammatory exercise by downregulating LPS-induced pro-inflammatory markers in murine macrophages. In comparison with ENVs remoted from turmeric alone (TENVs), TPENVs demonstrated enhanced percutaneous penetration in porcine pores and skin and had been immune to harsh gastrointestinal circumstances below simulated in vitro digestion. Intriguingly, this strategy additionally endowed TPENVs with ~8-fold greater curcumin content material in comparison with TENVs. Total, the method developed right here gives a easy, environmental-friendly and sustainable technique for one-pot isolation of curcumin with piperine in ENVs, in soluble and bioavailable kind. Given the demonstrated anti-inflammatory exercise of curcumin and piperine, TPENVs can be utilized as topical therapeutics for treating inflammatory pores and skin ailments the place intradermal supply of such bio-actives is important to extend their efficacy.