Objectives: Adipose-derived mesenchymal stem cell secretome is recognized for its anti-aging properties. is study investigated the optimal secretome administration for this purpose.Material and Methods: For 2 months at 2-week intervals, a total of 57 Indonesian women aged 35–59 years old were assigned to microneedling and one of these substrates: normal saline as control (C), unconcentrated secretome (S), or four-fold concentrated secretome (CS). e participants’ facial skin aging status was evaluated with the Janus-II measurement system and dermoscopy photoaging scale (DPAS). Statistical tests were used to analyze the data at the significance level of 0.05.Results: e CS group witnessed a significant decrement of ultraviolet spots at week 8 (P= 0.035). Intergroup comparison with control demonstrated spot reduction in subjects receiving CS at week 4 (P= 0.031) and porphyrin at week 6 (P= 0.007) and week 8 (P= 0.019). No marked discrepancies existed between the C and S groups in all Janus-II parameters. e total DPAS declined within all study groups (P< 0.001), but their average was comparable.Conclusion: CS treatment displayed positive responses for spots, porphyrin, and ultraviolet spots in senescent facial skin.