The increasing discharge of synthetic dyes into industrial wastewater necessitates sustainable and low-cost treatment strategies. This study valorizes orange seed powder (OSP), an abundant agro-food residue, as a novel biosorbent for Congo red (CR) removal through a combined experimental and molecular simulation approach. Raw OSP was prepared solely by drying and grinding, without chemical activation, emphasizing its practical applicability and environmental sustainability. Physicochemical characterization using FTIR, SEM, and EDX confirmed adsorption-induced structural and compositional changes. Batch experiments evaluated the effects of initial dye concentration, adsorbent dosage, pH, temperature, and contact time. Equilibrium data were well fitted by the Langmuir and Freundlich isotherm models (R² ≈ 0.99), with a maximum adsorption capacity of 258.39 mg g⁻¹ at 25 °C and pH 4, and a removal efficiency exceeding 99.55%. The adsorption kinetics followed a pseudo-second-order model, while intraparticle diffusion contributed to the rate-controlling mechanism, as indicated by the Weber–Morris model. OSP demonstrated excellent regeneration performance over five adsorption–desorption cycles, retaining more than 96% of its initial CR removal efficiency when regenerated with methanol. Grand Canonical Monte Carlo (GCMC) simulations revealed that adsorption is primarily driven by electrostatic interactions, hydrogen bonding, and π–π stacking interactions, in good agreement with the experimental findings. Overall, raw OSP represents an efficient, regenerable, and sustainable biosorbent, highlighting the originality of integrating experimental investigations with GCMC simulations for wastewater treatment applications.