To explore a potential link between resistance exercise and the gut-brain axis, this study examined the impact of resistance exercise on intestinal permeability, as indicated by lipopolysaccharide binding protein (LBP), and mood state in healthy adults. Sedentary participants (n = 20; 39.5 ± 12.1 y; 27.4 ± 5.3 kg/m) were randomly assigned to the resistance exercise (REX) or wait-listed control (CON) groups. REX participants strength trained 3× weekly (advancing from 45%-55% to 70%-80% 1RM for 3-4 sets over 8 weeks). Strength testing, evaluation of mood states, and collection of fasting blood occurred at baseline and weeks 4 and 8. At baseline, LBP concentrations were inversely correlated to all strength measures (r range: -0.48 to -0.57; p < 0.05). The gain in total strength [(split squat left + right)/2 + bench press] was 45% higher for REX versus CON participants (p = 0.019), and serum LBP concentrations fell 16% for REX participants and rose 9% in CON participants (p = 0.014). Mood was significantly improved by resistance training versus control (but this improvement was not related to changes in LBP; r = -0.001). These findings support a role for resistance exercise in improving mood state and intestinal barrier function, but more research is warranted to further explore the effects of resistance training on the gut-brain axis.