This review explores the potential of cannabinoids, particularly cannabidiol (CBD), in the treatment of acne vulgaris. Acne is a common skin condition affecting millions globally, with a complex pathogenesis involving sebum overproduction, hyperkeratinization, and bacterial colonization by Cutibacterium acnes. Traditional treatments include topical retinoids, antibiotics, and systemic therapies like isotretinoin, but these often have significant side effects, limiting patient compliance. Cannabinoids, including CBD, have shown promise due to their lipostatic, anti-inflammatory, antiproliferative, and antimicrobial properties. Preclinical studies indicate that CBD can regulate sebum production by modulating lipogenesis through TRPV4 ion channels, inhibit the proliferation of sebocytes, and reduce inflammation by suppressing pro-inflammatory cytokines and NF-κB signaling. Additionally, CBD exhibits antimicrobial activity against Cutibacterium acnes, potentially reducing bacterial overgrowth. Clinical trials are ongoing to evaluate the safety and efficacy of cannabinoids in acne treatment. Phytocannabinoids can be effectively applied topically, suggesting their potential as a novel, holistic approach to acne management. This review highlights the therapeutic potential of cannabinoids, emphasizing their ability to address multiple aspects of acne pathogenesis, offering a safer alternative to conventional treatments.This review explores the potential of cannabinoids, particularly cannabidiol (CBD), in the treatment of acne vulgaris. Acne is a common skin condition affecting millions globally, with a complex pathogenesis involving sebum overproduction, hyperkeratinization, and bacterial colonization by Cutibacterium acnes. Traditional treatments include topical retinoids, antibiotics, and systemic therapies like isotretinoin, but these often have significant side effects, limiting patient compliance. Cannabinoids, including CBD, have shown promise due to their lipostatic, anti-inflammatory, antiproliferative, and antimicrobial properties. Preclinical studies indicate that CBD can regulate sebum production by modulating lipogenesis through TRPV4 ion channels, inhibit the proliferation of sebocytes, and reduce inflammation by suppressing pro-inflammatory cytokines and NF-κB signaling. Additionally, CBD exhibits antimicrobial activity against Cutibacterium acnes, potentially reducing bacterial overgrowth. Clinical trials are ongoing to evaluate the safety and efficacy of cannabinoids in acne treatment. Phytocannabinoids can be effectively applied topically, suggesting their potential as a novel, holistic approach to acne management. This review highlights the therapeutic potential of cannabinoids, emphasizing their ability to address multiple aspects of acne pathogenesis, offering a safer alternative to conventional treatments.