Natural medicines are promising platforms for competent topical treatment modalities benefiting the cosmetic implementation and proffering solutions to the current remedies. Therefore, the objective of this study was to formulate syringic acid (SA), well-known for its multilateral anti-inflammatory, antimicrobial and antioxidant potentials, in newly developed linoleic acid (LA) transferosomes as an anti-acne nano-form remedy. Herein, LA was incorporated in transferosomes owing to its antimicrobial effect and dermal penetrability. Comprehensive appraisal through physicochemical, antioxidant and dermal deposition investigations was conducted. Clinical assessment was also performed in acne patients and compared with the marketed product (Adapalene® gel). The relevant investigations of the optimum formula indicated stable vesicles with a small-sized diameter (147.46 nm), surface charge (-26.86 mV), spherical architecture, reasonable entrapment (76.63%), considerable antioxidant activity (IC50 = 11.1 µg/mL) and remarkable skin deposition (78.72%).More importantly, LA based transferosomes enclosing SA exhibited inflammation lessening in acne sufferers as manifested by greater reduction in the total count of the acne lesions reaching 79.5% in contrast to Adapalene® gel with only 18.7% reduction in acne lesions. Interestingly, no irritation and erythema were reported for the proposed transferosomes. Inclusively, the cosmetic formulation practice could reap benefits of the development of such vesicles.