Soft tissue and organ defects or degeneration, caused by trauma, disease, and aging, lead to a great burden on human health, and soft tissue regeneration technology has shown great promise for addressing these challenges. In recent years, interdisciplinary efforts in the fields of biomechanics, mechanobiology and regenerative medicine have highlighted the critical roles of mechanical cues in microenvironment in regulating soft tissue regeneration. Despite these advances, there is still a lack of comprehensive understanding regarding the mechanical features of soft tissues in clinical practice, and the full potential of such mechanical features for diagnosing and treating soft tissue diseases has not been fully known. In this review, the concept of ‘mechanomedicine for soft tissue regeneration’ is proposed. Subsequently, the possible influence mechanisms of mechanical cues on soft tissue development and regeneration are systematically described from four distinct aspects, i.e., multi-scale biomechanics of soft tissues, mechanobiology of soft tissue regeneration, mechanomedicine techniques for soft tissue regeneration, and applications of mechanomedicine for soft tissue regeneration. Finally, the potential of mechanomedicine in clinical diagnosis of soft tissue diseases and soft tissue defect repair is discussed, thereby providing a new direction for the development of mechanomedicine for soft tissue regeneration.