The production of postbiotics for food applications has been growing in recent years owing to their biological potential and superior technological performance over probiotics. Their production involves the use of synthetic culture media, and in this work, we propose using sugarcane straw as a source of sugar and biological components and a sustainable alternative. Thus, this by-product was used as a substrate to produce a postbiotic extract using Saccharomyces cerevisiae as a fermentative microorganism. Sugarcane straw underwent a precedent saccharification step to release the fermentable sugars. The final extracts were characterized for their total content of sugars, phenolic compounds, organic acids, and their respective chromatographic profiles. Seventeen different polyphenols were identified with the predominance of three classes, the hydroxybenzoic acids, hydroxycinnamic acids, and flavonoids, where ferulic acid, 3,4-dihydroxybenzaldehyde, and 2,5-dihydroxybenzoic acid were most prevalent. The current work evaluated the potential use of this postbiotic extract for food applications, its antioxidant activity, gut microbiota modulatory effect, and intestinal anti-inflammatory potential. The resultant extracts showed considerable antioxidant activity and the ability to lower the pro-inflammatory mediators (i.e., interleukin 6, 8, and tumor necrosis factor-alpha) in Caco-2 cells. During the fecal fermentability assay, no modulatory effect was observed on the main beneficial bacteria, such as Lactobacillus and Bifidobacterium. Nevertheless, a significant increase in short-chain fatty acids, namely, acetate, propionate, butyrate, and valerate was observed. Moreover, the extract also demonstrated capacity to inhibit the proliferation of putrefactive bacteria such as Enterobacteriaceae. Finally, sustainable postbiotic extracts produced by S. cerevisiae fermentation using sugarcane straw as a substrate exhibited relevant biological properties with potential use as food and nutraceutical ingredients.