Stem cells have significant potential use in tissue regeneration, especially for treating cardiac diseases because of their multi-directional differentiation capability. By mimicking the in vivo physiological environment of native cardiomyocytes during their development and maturation, researchers have been able to induce pluripotent stem cell-derived cardiomyocytes (PSC-CMs) at high purity. However, the phenotype of these PSC-CMs is immature compared with that of adult cardiomyocytes. Various strategies have been explored to improve the maturity of PSC-CMs, such as long-term culturing, mechanical stimuli, chemical stimuli, and combinations of these strategies. Among these strategies, mechanical stretch as a key mechanical stimulus plays an important role in PSC-CM maturation. In this review, the optimal parameters of mechanical stretch, the effects of mechanical stretch on maturation of PSC-CMs, underlying molecular mechanisms as well as existing problems are discussed. Mechanical stretch is a powerful approach to promote the maturation of SC-CMs in terms of morphology, structure, and functionality. Nonetheless, further research efforts are needed to reach a satisfactory standard for clinical applications of PSC-CMs in treating cardiac diseases.

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