Sesame cake is an oil-industrial waste which contains a considerable amount of nutrients. In this study, steam explosion technology was introduced to modify the chemical composition, the protein structural characterization, and lignan profiles in sesame cake under mild conditions. The results showed that steam explosion treatment could effectively and significantly degrade the antinutritional factor phytate with 13.69–49.43% reduction and increase the protein yield of 2.69–9.16%, highly dependent on the severity of steam explosion conditions. Steam-exploded sesame protein has a disordered secondary structure and a balanced amino acid profile, leading to the improved nutritional value and bioavailability. The antioxidant activities of lignan extracts were dramatically promoted after treatment, along with the modified lignan profiles. Sesaminol glycosides were degraded a lot and significant amount of sesamol was detected and converted from sesamolin. Interestingly, large amount of sesaminol was produced by steam explosion treatment. It might be caused by the deglycosylation of sesaminol glycosides. These results show that steam explosion technology could be considered the ideal treatment method to improve the nutritional and pharmaceutical value of sesame cake.