This study explores tannin and caffeine, natural compounds with inherent antifungal properties, as scalable treatments to enhance the physical and mechanical performance of oriented strand board (OSB). Unlike previous research that primarily focused on durability, this work evaluates the effects of these bio-based treatments on leaching resistance, internal bond strength (IB), bending properties, water absorption, thickness swelling, and vertical density profile (VDP). The results demonstrate significant improvements over commercially available OSB, particularly in mechanical performance. Post-leaching, both treatments exhibited superior IB, with tannin-treated panels achieving the highest IB value (0.27 MPa). The bending analysis revealed that caffeine-treated panels that were not subjected to leaching achieved the highest modulus of rupture (MOR, 62.54 MPa) and modulus of elasticity (MOE, 10.36 GPa). Both treatments retained significantly higher MOR and MOE values post-leaching compared to the industrial reference and untreated panels. Water absorption and thickness swelling were comparable among tannin-treated, caffeine-treated, and untreated panels but were significantly lower than those of the industrial reference, which was included for general benchmarking purposes alongside the laboratory-made control. VDP analysis showed caffeine-treated panels had the lowest density prior to leaching, whereas tannin-treated panels maintained the highest density after leaching. These findings highlight tannin and caffeine as effective and scalable treatments, providing a sustainable alternative as functional additives for industrial engineered wood product manufacturing.