The Fermi-Hubbard model (FHM) is a simple yet rich model of strongly interacting electrons with complex dynamics and a variety of emerging quantum phases. These properties make it a compelling target for digital quantum simulation. Trotterization-based quantum simulations have shown promise, but implementations on current hardware are limited by noise, necessitating error mitigation techniques like circuit optimization and post-selection. A mapping of the FHM to a Z2 LGT was recently proposed that restricts the dynamics to a subspace protected by additional symmetries, and its ability for post-selection error mitigation was verified through noisy classical simulations. In this work, we propose and demonstrate a suite of algorithm-hardware co-design strategies on a trapped-ion quantum computer, targeting two key aspects of NISQ-era quantum simulation: circuit compilation and error mitigation. In particular, a novel combination of iteratively preconditioned gradient descent (IPG) and subsystem von Neumann Entropy compression reduces the 2-qubit gate count of FHM quantum simulation by 35