Background <p>Lower eyelid wrinkles pose a persistent challenge in facial rejuvenation. Layered autologous fat grafting using Coleman fat, SVF-gel, and nanofat offers a regenerative approach with potential synergistic benefits.</p> Objective <p>To assess the efficacy and safety of this layered technique in patients with mild and severe lower eyelid wrinkles.</p> Methods <p>Sixty patients presenting with lower eyelid wrinkles were divided into mild and severe groups according to baseline wrinkle severity. All patients received layered injections of Coleman fat, SVF-gel, and nanofat. Outcomes were evaluated using standardized wrinkle scores, patient satisfaction ratings, and VISIA imaging system analysis, both preoperatively and at 12 months postoperatively.</p> Results <p>Significant improvements in wrinkle scores, VISIA analysis results, and patient satisfaction were observed in both groups at 12 months. Greater wrinkle reduction and satisfaction were achieved in the mild group compared to the severe group. No serious complications were reported.</p> Conclusions <p>Layered injection of Coleman fat, SVF-gel, and nanofat is a safe and effective therapeutic approach for lower eyelid wrinkles. It offers superior and more predictable rejuvenation, particularly for patients with mild wrinkles, supporting its role as an advanced option for lower eyelid wrinkle treatment.</p> Level of Evidence III <p>Therapeutic study. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors <a href="https://www.springer.com/00266">www.springer.com/00266</a>.</p>