The functional interaction of regulatory mechanisms that manage total centre of mass (CoM) energy, frontal plane whole-body angular momentum and mediolateral margin of stability (MoS) during hole negotiation gait was investigated. Joint kinematics, leg posture, total CoM energy, frontal plane whole-body angular momentum, mediolateral MoS and muscle activation patterns of seven bilateral lower leg muscles were assessed in 18 participants. During hole negotiation, we found an increase in the peak-to-peak range of total CoM energy and frontal plane whole-body angular momentum during the preparation, hole and recovery steps, and a decrease in mediolateral MoS at touch-down during the preparation and hole steps compared to level walking, providing evidence of an increased challenge in stability control. Anticipatory adjustments in CoM trajectories, joint kinematics and muscle activation patterns regulated mechanisms that primarily supported the management of total CoM energy at the expense of whole-body angular momentum in the frontal plane. We identified an anticipatory foot placement strategy during the step in the hole that significantly reduced the moment arm of the vertical ground reaction force (p = 0.011, d = 0.81), thereby favouring the control of frontal plane whole-body angular momentum. Conversely, this foot placement strategy significantly reduced (p < 0.001, d = 1.05) the mediolateral MoS. The mutual influence between the regulatory mechanisms that control total CoM energy, frontal plane angular momentum and mediolateral MoS represent trade-offs rooted in the nature of the hole negotiation gait and demonstrate the challenge of moving on uneven terrain.