This project focuses on the synthesis of a novel biocompatible nanocatalyst, and evaluates its catalytic performance in the three-component synthesis of xanthene derivatives. To achieve this, Zeolite-Y was functionalized with the basic amino acid L-arginine through a linker agent, 3-chloropropyltriethoxysilane (Arg@Zeolite-Y). The structural features of the nanocatalyst were confirmed using various characterization techniques including Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), Brunauer–Emmett–Teller surface area analysis (BET), field emission scanning electron microscopy (FE-SEM), thermogravimetric analysis (TGA), and energy-dispersive X-ray spectroscopy (EDX). The catalytic efficiency of this nanocomposite was assessed in the green synthesis of xanthene compounds. Initially, the feasibility of the reaction was investigated via a one-pot cyclization of dimedone and benzaldehyde under different reaction conditions. Subsequently, the general applicability of the optimized reaction for the synthesis of various xanthene derivatives was demonstrated. The key advantages of this project include the use of a non-toxic, recyclable, biocompatible nanocatalyst, and solvent-free green conditions. Additional benefits comprise the cost-effective preparation of the nanocatalyst, ease of product isolation, high yield, and reduced reaction time.