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Several formulations have been developed in the current era using liposomes and niosomes as vesicular carriers, which have proven useful in oral drug delivery; nevertheless, their use is limited due to their gastrointestinal environment, including pH, enzymes, and bile salts. To overcome these difficulties, researchers are working on finding ways to improve the efficacy and stability of vesicles. Therefore bilosomes have been developed as promising vesicular carriers with the potential to deliver oral vaccines, parenteral and transdermal targeted drug delivery. In addition to incorporating hydrophilic as well as lipophilic drugs into vesicles, bilosomes are considered one of the most effective methods for enhancing bioavailability and efficacy. Bile acid-based bilosomes are rapidly growing in the current research areas and are expected to provide multiple applications in the pharmaceutical and biomedical fields that will occur in the future with bile salts. This paper briefly introduces the bilosomes of a new generation (structure), their mechanism of action, stability, physicochemical properties, and potential biomedical applications including in oral immunization. Furthermore, surface-engineered bilosomes are more effective than bare bilosomes in various animal models, but clinical trials are needed to assess their safety and efficacy. There is also a need for more research on scaling-up factors for commercializing bilosomal systems. [ABSTRACT FROM AUTHOR]