We investigated the potential use of coconut water to supplement potato dextrose broth (PDB) in the production of Ophiocordyceps sinensis CS1197 by submerged cultivation. The basal PDB medium was modified by supplementation with tender coconut water (TCW) and mature coconut water (MCW) at 10% and 5% (v/v), respectively; these mixtures were cultured at 28°C for 14 days, with a pH of 7 and an inoculum volume of 10%. The addition of optimized levels of TCW and MCW improved the biomass yield by 2.2- and 2.5-fold, respectively, and adenosine, cordycepin, and polysaccharide content by 58% and 69%, 50% and 55%, and 19% and 27%, respectively. Antioxidant and cholesterol esterase (CE) inhibitory activities of the aqueous extract from O. sinensis CS1197 mycelia supplemented with TCW and MCW were high compared with those of the control, indicating that coconut water has a positive correlation with the enhanced antioxidant and CE inhibitory activities. These antioxidant and CE inhibitory responses were dependent on concentration, and the larger amounts of bioactives in O. sinensis CS1197 are beneficial in pharmaceutical formulations.