The upcycling of food processing byproducts offers significant environmental and economic benefits. In this study, the effects of lactic acid bacteria (Weissella cibaria MFST for FPSK) and yeast (Issatchenkia orientalis MFST for FPSM) fermentation on the polyphenol composition and antioxidant activity of persimmon sludge were explored. TLC and HPLC analyses confirmed significantly higher polyphenol and flavonoid contents in fermented samples (FPSK and FPSM) than in the non-fermented control (PS). FPSM exhibited higher levels of key bioactive polyphenols than FPSK, indicating that yeast fermentation was the most effective at hydrolyzing polyphenolic glycosides and enhancing bioavailability. The increased phenolic release in FPSM correlated with higher antioxidant activity, as demonstrated by DPPH, ABTS, and reducing power assays. Differences in pH and microbial metabolic factors probably influenced enzymatic activity and polyphenol transformation. These findings highlight yeast fermentation as a promising strategy for enhancing the functional properties of persimmon sludge, thereby supporting its use in functional foods and natural antioxidants.