This paper presents an application of topology optimization and response surface method to optimize the geometry of a bicycle crank arm and the experimental validation of it. This is purposely to reduce the crank arm mass and create a preliminary design of a lightweight structure necessary for the high-performance bicycle development. A three-dimensional bike crank arm model was made in the SpaceClaim software followed by a static finite element analysis using ANSYS Workbench 2019 R1. A multiple cycling load was applied simultaneously in seven crank angles of 30, 45, 60, 90, 120, 135, and 150° relative to the horizontal position to create the multiple loads to the crank. From there, topology optimization was then conducted to investigate the effect of mass constraint, stress constraint, angle of cycling, and crank materials on the topological pattern result. To minimize stress concentration at corners, a shape optimization using the response surface method was conducted and obtained the final geometry. From the result, it is shown that both optimization methods not only successfully reduce the crank arm mass and provide several optimum design options but also are able to reduce the maximum stress in the crank arm up to 20% after the optimization process. The experimental validation using a newly developed wireless measurement system shows a considerable agreement to the numerical results.