This study explores the impact of fly ash (FA) filler on the mechanical, morphological, and water absorption properties of pineapple leaf fibre (PALF)-reinforced epoxy composites for biomedical applications. PALF, sourced from abundant agricultural waste, offers a sustainable alternative to synthetic fibres. Employing the hand layup process, varying wt% of FA (3%, 6%, and 9%) are incorporated into PALF-reinforced epoxy composites with different PALF concentrations (10%, 20%, and 30%). Mechanical assessments, including impact, flexural, and tensile strength, reveal that the introduction of up to 6 wt% FA enhances tensile strength by 65.3%, reaching its peak at this concentration. Flexural strength also improves by 31.9% with 6 wt% FA, while impact resistance reaches its maximum (74.18% improvement) at 9 wt% FA. Water absorption measurements demonstrate a decrease with increased FA content and exposure period, indicating enhanced water resistance. Scanning electron microscopy confirms the uniform distribution of FA, contributing to improved mechanical characteristics and water resistance. Optimality tests using Taguchi and response surface methodology (RSM) further confirm the experimental outcomes, emphasizing the potential of FA to enhance natural fibre-reinforced composites. This research suggests FA as a promising filler to elevate mechanical performance and water resistance in environmentally friendly composites.