Coenzyme Q10 (CoQ10) is a naturally produced organic molecule which acts as an antioxidant agent, including in skin anti-ageing, and plays a major role in the social determinants of health. However, its level in the body will decrease during ageing. Therefore, an external supplement is required to repair damaged skin, especially the skin dermis layer. This study aims to evaluate the use of a protransfersomal emulgel to improve the skin delivery and stability of CoQ10 which demonstrates low water solubility, poor permeability and instability. CoQ10 was initially dissolved in oleic acid at a weight ratio of 1:56. Protransfersome was then loaded with CoQ10 (Protransf-CoQ10) and prepared using a composition of L-α-Phosphatidylcholine and Tween 80 at a molar ratio of 85:15. The Protransf-CoQ10 was dispersed in an emulgel base consisting of Tween 80 and Span 80 to produce Protransf-CoQ10 emulgel. The in vivo studies of anti-aging activity and irritability were further evaluated by applying daily 200 mg of emulgels twice a day to a 4 cm2 section on the back of a UV-ray aging-induced male Balb/c mouse 20 min before irradiation. The results showed that Protransf-CoQ10 could transform into transfersomal vesicles with particle sizes of approximately 201.5 ± 6.1 nm and a zeta potential of − 11.26 ± 5.14 mV. The dispersion of Protransf-CoQ10 into emulgel base resulted in stable Protransf-CoQ10 Emulgel during 28 days of observation at low temperatures. Moreover, the in vivo study revealed that Protransf-CoQ10 Emulgel successfully increases the collagen density and number of fibroblast cells in UV radiation skin-aged induced-mice which reflects its potential for repairing the skin ageing process. In addition, the 24-h topical application of Protransf-CoQ10 Emulgel showed that no erythema or skin rash was observed during the study. In conclusion, loading CoQ10 into protransfersomal Emulgel successfully enhanced the stability and anti-ageing efficacy enabling its potential use as anti-ageing cosmetics.