Natural and synthetic fibers offer a multitude of advantages within the automotive sector, primarily due to their lightweight properties, including appealing characteristics such as adequate mechanical strength, low density, improved acoustic–thermal insulation, cost-effectiveness, and ready availability. In this study, we aimed to strengthen epoxy-based composites with natural and synthetic fibers using bamboo and glass, respectively. Additionally, the reinforcement processing of this hybrid composite material was optimized using a Taguchi L9 (nine experimental runs) orthogonal array design with linear modeling through the Design of Experiment (DoE) principles. The fibers were alkali-treated with sodium hydroxide (NaOH), and the composites were manufactured through the hand lay-up process at ambient temperature and characterized comprehensively using ASTM standard methods. The experimental results of the bamboo–glass fiber composite materials presented a significantly high tensile strength of 232.1 MPa and an optimum flexural strength of 536.33 MPa. Based on the overall Taguchi and linear modeling analysis, the NaOH treatment, fiber content, and epoxy resin concentration were optimized. These findings reveal that the ideal combination consists of 20% fiber content, 8% NaOH treatment, and 65% epoxy resin concentration. The statistical method Analysis of Variance (ANOVA) was employed to confirm the significance of these factors. The integration of the amount (%) of bamboo fiber used played a pivotal role in influencing the mechanical properties of this hybrid composite. Overall, this study demonstrates that the reinforcement of natural fiber with polymeric material composites on epoxy enhanced the composite characteristics and quality. Therefore, this bamboo–glass–epoxy-based composite can be recommended for lightweight structural applications, especially in the automotive sector, in the future.