Objectives: To systematically review and synthesize available clinical and experimental evidence on the effects of beta-blockers in the treatment of acne vulgaris. Methods: A thorough search across four databases identified 412 relevant publications. After removing duplicates using Rayyan QCRI and screening for relevance, the search yielded 209 publications, of which 29 full-text articles were reviewed, and 5 met the eligibility criteria for evidence synthesis. Results: We included 5 studies with a total of 205 patients and 140 (68.3%) were females. The findings consistently indicated beneficial effects in the management of non-inflammatory acne lesions, post-acne erythema, and acne scarring—particularly when used in conjunction with fractional CO₂ laser therapy. Across all studies, the treatment was well tolerated with no significant adverse effects reported. Conclusion: Topical beta-blockers, especially timolol maleate 0.5%, represent a promising adjunct in the treatment of acne vulgaris. Their clinical effectiveness, safety, and affordability make them a compelling option, particularly for patients unresponsive to or intolerant of standard therapies. Further randomized trials are necessary to validate their role and establish standardized treatment protocols.