Stochastic thermodynamics has largely succeeded in characterizing both equilibrium and far-from-equilibrium phenomena. Yet many opportunities remain for application to mesoscopic complex systems-especially biological ones-whose effective dynamics often violate detailed balance and whose microscopic degrees of freedom are often unknown or intractable. After reviewing excess and housekeeping energetics-the adaptive and homeostatic components of a system's dissipation-we extend stochastic thermodynamics with a trajectory class fluctuation theorem for nonequilibrium steady-state, nondetailed-balanced complex systems. We then take up the neurobiological examples of voltage-gated sodium and potassium ion channels to apply and illustrate the theory, elucidating their nonequilibrium behavior under a biophysically plausible action potential drive. These results uncover challenges for future experiments and highlight the progress possible understanding the thermodynamics of complex systems-without exhaustive knowledge of every underlying degree of freedom.