Wood is susceptible to termite degradation, necessitating the development of effective and sustainable preservative systems. This study evaluates the termite resistance of wood treated with guayule resin as a bio-based preservative against Coptotermes formosanus, with emphasis on the effects of resin concentration, species, and carrier system. Yellow poplar and southern pine specimens were treated via vacuum impregnation with guayule resin at 0.5% and 5% concentrations using acetone and toluene as solvents and subjected to a no-choice termite test following AWPA Standard E1-23. Termite resistance was assessed through mass loss, visual damage ratings, and termite mortality, and analyzed using two-way ANOVA. A significant interaction between wood species and resin concentration was observed. The lowest mass loss occurred at 5% guayule resin in toluene for both species, with a more pronounced improvement in southern pine, which exhibited greater susceptibility to termite attack than yellow poplar. Termite mortality remained low across all treatments, indicating that guayule resin primarily functions as an antifeedant rather than a toxicant. These results demonstrate that guayule resin can reduce termite feeding damage at relatively low concentrations, highlighting its potential as a sustainable, cost-effective alternative to conventional wood preservatives.