Biomass harvesting and drying represent the most energy-intensive stages in algal biomass processing. Despite the availability of various technologies at the laboratory scale, certain methods, such as centrifugation or freeze-drying, become prohibitively expensive when scaled up. The primary objective of this study was to identify the optimal method for harvesting and drying algal biomass while minimizing the impact on metabolite content, encompassing carbohydrates, proteins, and lipids. To achieve this goal, an I-optimal design incorporating four variables and two levels was employed to determine the most efficient methods. These findings revealed that electroflotation surpasses chemical flocculation as the preferred method for harvesting, while dewatering is more efficient than convective oven drying is. Further optimization efforts indicated that employing low temperatures and extended durations (56°C and 41 hours, respectively) constitute the optimal strategy for reducing moisture in the biomass while simultaneously enhancing the extraction of metabolites. These results present a more sustainable and economically viable approach to harvesting and drying substantial quantities of algal culture, with a diminished impact on metabolite composition.