This study investigated physical activity (PA) and sedentary time (SED) in relation to hippocampal gray matter volume (GMV) in pediatric overweight/obesity. Ninety-three children (10 ± 1 year) were classified as overweight, obesity type I, or type II–III. PA was assessed with non-dominant wrist accelerometers. GMV was acquired by magnetic resonance imaging (MRI). Neither PA nor SED associated with GMV in the hippocampus in the whole sample (p > 0.05). However, we found some evidence of moderation by weight status (p < 0.150). Moderate-to-vigorous PA (MVPA) positively associated with GMV in the right hippocampus in obesity type I (B = 5.62, p = 0.017), which remained when considering SED, light PA, and sleep using compositional data (γ = 375.3, p = 0.04). Compositional models also depicted a negative association of SED relative to the remaining behaviors with GMV in the right hippocampus in overweight (γ = −1838.4, p = 0.038). Reallocating 20 min/day of SED to MVPA was associated with 100 mm3 GMV in the right hippocampus in obesity type I. Multivariate pattern analysis showed a negative-to-positive association pattern between PA of increasing intensity and GMV in the right hippocampus in obesity type II–III. Our findings support that reducing SED and increasing MVPA are associated with greater GMV in the right hippocampus in pediatric overweight/obesity. Further studies should corroborate our findings.