This study combined the advantages of a serial manipulator and a pneumatic muscle actuator—large workspace and compliance, respectively—to develop a compliant six-degree-of-freedom (6-DOF) serial manipulator and design an energy-efficient safety controller. In terms of kinematics analysis, this study applied the Denavit-Hartenberg transformation matrix to solve the manipulator's forward and inverse kinematics equations, analyze the workspace, and verify the terminal trajectory. By doing so, this study ensured that the system designed met the desired workspace of the manipulator. In terms of controller design, the objective was to improve the control of the 6-DOF serial manipulator driven by pneumatic muscles and reduce its energy consumption. This study incorporated fractional calculus characterized by fluid properties into a safe and novel proxy-based sliding mode control (NPSMC) proposed at the laboratory. The fractional-order proxy-based sliding mode control (FOPSMC) design method was proposed based on a fractional-order extended state observer (FOESO). Fractional-order Lyapunov direct method was applied to verify the stability of the designed controller. This study reformulated a compliant 6-DOF serial manipulator for the experiment using NPSMC and FOESO-FOPSMC for manipulator motion control. According to the experimental results, the optimized design of the compliant 6-DOF serial manipulator demonstrated a higher power-to-weight ratio and larger workspace compared with the original pneumatic muscle actuator. Trajectory tracking accuracy and energy efficiency were superior under the compensation of FOESO-FOPSMC than under the compensation of NPSMC.