This study aimed to pioneer the development of an innovative, ecofriendly, and chrome-free tanning agent, with a focus on promoting sustainable practices in ecological leather production. Two novel biomass-derived tanning agents, namely, β-TCD and β-GCD, were synthesized through a one-pot grafting process involving environmentally friendly epoxy monomers: triglycidyl isocyanurate (TGIC) and glycerol triglycidyl ether (GTE). Characterization through various analytical methods, including FTIR, 1 H NMR, XPS, GPC, SEM, and TGA, confirmed the successful grafting of TGIC and GTE onto β-cyclodextrin (β-CD) backbones. The resulting β-TCD and β-GCD exhibited notable epoxide values of 0.349 and 0.388 mol/100 g, respectively, along with a broader molecular weight distribution of intermediates. These newly developed tanning agents, β-TCD and β-GCD, were then applied in depickling goatskin tanning experiments. Results indicated that the crust leather tanned with β-TCD and β-GCD displayed favorable thermal stability, with shrinkage temperatures reaching 84 and 82 °C, respectively. Moreover, the thickening rates of the leather exceeded 40%. The crust leathers tanned with β-TCD, and β-GCD demonstrated excellent physical and mechanical properties, as well as notable resistance to yellowing compared to conventional commercial chrome-free tanning agents like TWS and F-90. Overall, this research emphasizes the efficacy of natural cyclodextrin materials as potent and environmentally friendly alternatives to chromium-based tanning agents, showcasing their significant potential in advancing sustainable and cleaner practices in leather production.