Aims This study aims to evaluate the impact of solid-state fermentation (SSF) by Trichoderma reesei on the phenolic content, antioxidant and antimicrobial activities of garden cress seeds (GCS). Methods and Results The factorial statistical design was employed to optimize the SSF conditions, incubation time, pH, temperature and moisture, for maximum production of the phenolic content and microbial carbohydrate-cleaving enzymes from GCS. The total phenolic content significantly increased from unfermented GCS (401 mg gallic acid equivalent (GAE) 100 g(-1)) to fermented GCS (3600 mg GAE 100 g(-1)) by ninefold. The total antioxidant activity significantly increased in fermented GCS. Fifteen phenolic compounds were detected in fermented GCS with high concentrations compared to 14 in unfermented GCS using high-performance liquid chromatography. A strong correlation between the production of the carbohydrate-cleaving enzymes and the phenolic content of fermented GCS was observed. The phenolic compounds of fermented GCS showed higher antimicrobial activity. Conclusions The fermented GCS is a powerful source of phenolic compounds with high antioxidant potentials, which can be used as dietary supplement and antimicrobial agent. Significance and Impact of the Study Solid-state fermentation is a promising technique used for production of added-value bioactive compounds. SSF increased the total phenolic content and antioxidant activity of GCS several folds compared to germination process, which recently studied.