Abstract <p>Degenerative disc disease (DDD) is a prevalent condition contributing significantly to low back pain and disability. Traditional treatments offer only symptomatic relief, leading to the exploration of regenerative therapies. Among them, adipose stem cells (ASCs) have emerged as a promising candidate for intervertebral disc (IVD) regeneration due to their accessibility, multipotency, and paracrine effects. The aim of this review was to evaluate the potential of ASCs in regenerating IVDs affected by DDD. In vitro studies have demonstrated the ability of ASCs to differentiate into nucleus pulposus–like cells, crucial for IVD function, especially when influenced by growth factors like TGF-β and GDFs. In vivo studies have further supported the regenerative potential of ASCs, showing improved disc hydration, structural restoration, and ECM production. Some clinical trials have been conducted, and most of them have described the safe application of ASCs for reducing pain and enhancing disc function. However, challenges such as delivery methods, cell viability, and regulatory hurdles must be addressed. In conclusion, ASC-based approaches demonstrated substantial regenerative promise across experimental models and early-phase clinical trials. Continued efforts are required to overcome translational barriers and ensure reproducible, long-term therapeutic outcomes in human DDD treatment. </p> Lay Summary <p>Degenerative disc disease (DDD) is a major cause of chronic back pain and disability. Traditional treatments like painkillers and surgery only manage symptoms without repairing the damaged discs. This review explores the potential of adipose-derived stem cells (ASCs) to regenerate intervertebral discs. ASCs can reduce inflammation, improve disc hydration, and restore tissue structure. In clinical and animal studies, ASCs have shown promising results in regenerating damaged discs, and early clinical trials suggest they are safe. However, challenges like delivery methods and cell survival remain. Future research aims to enhance ASC therapy for better outcomes in treating DDD. Future Research. Future works should focus on optimizing ASC-based therapies by improving cell delivery methods, enhancing cell survival, and exploring genetic modifications. Advanced biomaterial scaffolds and microsphere-based delivery systems could enhance regenerative potential. Clinical trials are needed to establish long-term safety, efficacy, and regulatory approval for ASC-based treatments in DDD.</p>