<p>Organ regeneration and manufacturing are promising new research directions in the life sciences. Stem cells and their niches, which exist in most adult organs, play a central role in organ development, homeostasis, and regeneration. Although considerable advances have been made in stem cell-mediated organ regeneration and manufacturing in recent decades, their clinical effectiveness remains unsatisfactory. Stem cell niches comprise a dynamic microenvironment that supports stem cells throughout their lifetime and are critical to stem cell fate. Based on recent research on stem cell niches, tremendous progress has been made in organ regeneration and manufacturing <i>in vivo</i> and <i>in vitro</i>. In this review, we discuss recent advances in the composition and function of stem cell niches during regeneration. We also discuss stem cell niche remodeling using cell-cell interaction, extracellular matrix (ECM) reconstruction, cell-ECM interaction, and key signaling-based niche strategies to promote endogenous tooth, gastrointestinal tract, and liver regeneration and its application in organoids and organoid-on-chip construction.</p>