Topical delivery of bioactives from natural sources offers several advantages over oral delivery, including avoidance of first-pass metabolism, specific delivery of the active agents at the target site, and enhanced therapeutic efficacy. However, the topical delivery of natural bioactives faces several hiccups in terms of permeation across the dermal barrier at different levels, including the stratum corneum, epidermis, dermis, and hypodermis. Nanomedicine-mediated delivery of bioactives is rapidly gaining popularity for topical delivery, because of its interactions with the skin tissue at subatomic levels. The same can be successfully accomplished using vesicular carriers such as liposomes, niosomes, ethosomes, hyalurosomes, and transfersomes as the potential novel drug carriers to overcome the challenges for topical delivery of bioactives. These vesicular systems have demonstrated enormous potential for topical delivery, owing to their uniqueness to facilitate the interactions at the barrier membranes. The chapter summarizes the emerging efforts in the topical delivery of various plant bioactives employing nanovesicular delivery systems with special emphasis on lipidic vesicular systems.