Hypoxia stress may affect the fish intestine and thereby threaten the growth and survival of the fish. Teprenone is a clinically effective agent in protecting gastrointestinal mucosa. This study aims to assess the effect of teprenone in the intestine of Chinese sea bass Lateolabrax maculatus under intermittent hypoxic stress. L. maculatus juveniles were either raised under intermittent hypoxic condition or normal condition (NC). Part of the hypoxic-intervened fish were treated with teprenone at different concentrations (HTs), and the rest were regarded as hypoxic control (HC). Histological analysis was performed on the epithelial tissue of the fish intestine. High-throughput sequencing technology was used to analyze the diversity and composition of the microbial community in L. maculatus intestine. Reduced villi length and goblet cell, exfoliated enterocyte, and improper arrangement of villi were observed in HC compared with NC and HTs. Proteobacteria, Firmicutes, and Bacteroidetes represented the most abundant phyla in each sample. Significantly higher microbial diversity was detected in HC compared with NC (P < 0.05). At the phylum level, HC presented significantly decreased relative abundance of Proteobacteria, and significantly increased relative abundance of Bacteroidetes, Chloroflex, and Cyanobacteria compared with NC (P < 0.05). At the class level, HC showed significantly reduced relative abundance of Alphaproteobacteria and Bacilli, and significantly increased relative abundance of Clostridia, Gammaproteobacteria, and Bacteroides (P < 0.05). Teprenone protects the intestine from epithelial damages and maintains the microbial harmony in L. maculatus under intermittent hypoxic stress.