Cottonseed hull (CSH), typical agro-industrial byproduct, is widely valorized as ruminant alternative feeds, but many constraints including extensive anti-nutritional factors and indigenous hazardous microflora are still reasonably unsolved. This study proposed a novel strategy that valorizes unautoclaved CSH as ruminant alternative feeds via solid-state fermentation (SSF), where feasibility and microbial mechanism were roundly investigated. The SSF of raw CSH (R group, proposed in this study) was compared with autoclaved CSH (M group, prevalent strategy) based on physicochemical properties, chemical functionalities, and superficial structures. Compared to M group, R group though has exhibited near detoxification effect of polyphenols (81.7% free gossypol (FG) and 62.2% condensed tannin (CT), both below threshold values) after SSF, yet the accumulation of crude protein and fat has been higher (109.3 and 51.0 g/kg dry matter, respectively). Metagenomic analyses indicated the indigenous hazardous microorganisms and antibiotic-resistance genes were prevented from amplification in R group. More importantly, Pleurotus was the keystone contributor to functional gene sets of degrading polyphenols (FG and CT) and lignin during SSF in R group; furthermore, CAZyme gene sets associated with polysaccharide degradation were primarily derived from bacterial communities ( Cellulomonas , and Stenotrophomonas , et al.). Ultimately, microbial SSF of raw CSH can be a feasible strategy with minimum facility investment and energy consumption, thus expediting CSH valorization in feedstock industries and the sustainable bio-economy in developing countries. • SSF valorizing raw cottonseed hull (CSH) as ruminant alternative feeds is feasible. • This strategy facilitates the sustainable bio-economy. • Polyphenols content declined to safe threshold during SSF. • SSF is resilient to animal pathogens and the transfer of antibiotic resistance genes. • Functional gene set about polyphenol and lignin degradation is traced from Pleurotus .