Acne vulgaris is a common skin condition that primarily affects adolescents and significantly impacts their quality of life. It ranks as the 8th most prevalent disease globally, with an estimated prevalence of 9.4% in the global population. Despite the availability of various treatment options, acne remains a distressing issue for adolescents due to the presence of disfiguring marks and scars. This study aimed to evaluate the safety and efficacy of a topical Unani drug, Shoniz (Nigella sativa), and Sirka (Grape vinegar), in the management of acne. Methods: A randomized, open-label, standard controlled study was conducted with 60 patients diagnosed with acne, aged between 10 to 40 years, who met the inclusion criteria. The participants were randomly assigned to receive either local application of Shoniz (Nigella sativa) and Sirka (Grape vinegar) or Benzoyl peroxide 5% cream for a duration of 56 days. The study was conducted after obtaining ethical approval (Reference no. RRIUM/KU/2018-19/Tech/IEC dated 29/3/2019) and was registered in the Clinical Trials Registry India (CTRI) with registration number CTRI/2020/06/025718. Acne severity was assessed using a grading scale at baseline (day 0) and on days 15, 29, 43, and 57. Baseline investigations were conducted before and after the treatment period. Results: Objective parameters showed significant improvement within both the test and control groups (p-value < 0.0001). There was no significant difference between the test and control groups in terms of lesion improvement, indicating that the test drug (Nigella sativa paste with Sirka) was equally effective in treating acne compared to the control drug (Benzoyl peroxide cream). However, the test drug had a more significant effect on papules compared to the control drug (p-value < 0.001). Conclusion: The local application of Shoniz (Nigella sativa) and Sirka (Grape vinegar) in paste form demonstrated effectiveness in improving acne and can be considered as a viable treatment option for this condition. The treatment was generally well tolerated by the participants.