Background: Chemical peel is a cosmetic procedure that is becoming a popular modality in treating acne vulgaris (AV). Mandelic acid (MA) is an upcoming peeling agent for AV due to its anti-inflammatory and antibacterial traits. Hence, it is worthwhile to appraise this newer agent’s effectiveness and safety profile and compare it with a more traditional and established peeling agent, salicylic acid (SA), in the treatment of AV. Aims: The aim of this study was to compare the efficacy of 40% MA with 30% SA peels in south Indian patients suffering from mild-to-moderate facial AV. Materials and Methods: One hundred patients suffering from mild-to-moderate facial AV were distributed randomly into two groups of 50 each, with group A receiving 40% MA peel and group B receiving 30% SA peel at an interval of two weeks for six sessions. The duration of the study was twelve weeks. Clinical pictures and Michaelsson acne scores (MAS) were used to evaluate the effectiveness of treatment objectively. Adverse effects of both the peeling agents were also noted. Statistical Analysis Used: A value of P ≤ 0.05 was considered significant. Results: Overall, there was no significant difference in the efficacy between the two peels. However, adverse effects were slightly higher with SA peel. Conclusions: The 40% MA peel was equally effective as 30% SA peel in mild-to-moderate facial AV. However, safety profile and tolerability were better in the MA peel group than the SA peel group. © 2024 Elsevier B.V., All rights reserved.