The disposal of leather waste has always been a huge challenge facing the tannery. Thus, the effectiveconversion of leather waste into value-added products can help the leather industry achieve green andsustainable development. In the paper, we utilized collagen hydrolysate (CH) obtained from leatherwaste as a protein retarder for gypsum and the effect of CH on the setting, hydration and crystallizationprocess of gypsum was analyzed. The results showed the addition of CH delayed the increase in hydrationdegree and release of hydration heat during the hydration process of gypsum, and this delay action wasmore remarkable as more CH was introduced. Moreover, CH could postpone the crystallization of dihydrategypsum from a micro perspective. TG/DSC, FTIR, XRD, and SEM analysis indicated that the presenceof CH inhibited the hydration reaction hemihydrate gypsum and the formation of dihydrate gypsum butover time the hemihydrate gypsum was completely hydrated at last. Finally, the retardation mechanismof CH on the gypsum was investigated by adsorption and zeta potential measurements. Adsorption andzeta potential measurement results demonstrated that CH could inhibit the hydration process of hemihydrategypsum by adsorbing on the gypsum particle, thereby achieving the retarding effect.