This study explored the enhancement of exopolysaccharide (EPS) production by Ganoderma lucidum through bidirectional liquid fermentation, employing Clinacanthus nutans (Burm. f.) Lindau leaves as a medicinal substrate. The optimal concentration of C. nutans leaf powder was determined to be 6 g/L, resulting in a significant increase in both mycelial biomass (61.78%) and EPS yield (116.6%). Structural analyses indicated that the EPS supplemented with C. nutans underwent notable modifications. Fourier-transform infrared spectroscopy suggested the introduction of potential carbonyl groups and a shift in glycosidic linkage configuration. Monosaccharide composition analysis revealed a significant transition from a glucose-dominated profile in the control to a galactose-rich, more diverse profile, including uronic acids and amino sugars, in the experimental group. High-performance gel permeation chromatography demonstrated a transformation from a low, homogeneous molecular weight (4.7 kDa) to a heterogeneous, bimodal distribution featuring a prominent high-molecular-weight fraction (38.5 kDa). Consequently, the modified EPS exhibited significantly enhanced antioxidant activities, with scavenging rates for DPPH, hydroxyl, and ABTS radicals increasing to 55.5%, 35.1%, and 88.0%, respectively, at a concentration of 2 mg/mL. These findings demonstrate that C. nutans is an effective supplement for modulating the fermentation process of G. lucidum, not only boosting EPS production but also tailoring its structural characteristics to obtain polysaccharides with superior bioactivities, highlighting its potential in functional food and nutraceutical applications.