Prostate cancer is the most common noncutaneous cancer and the second leading cause of cancer deaths among American men. Statins and omega-3 are two medications recently found to correlate with prostate cancer risk and aggressiveness, but the observed associations are complex and controversial. We therefore explore the novel application of radiomics in studying statin and omega-3 usage in prostate cancer patients. On MRIs of 91 prostate cancer patients, two regions of interest (ROIs), the whole prostate and the peripheral region of the prostate, were manually segmented. From each ROI, 944 radiomic features were extracted after field bias correction and normalization. Heatmaps were generated to study the radiomic feature patterns against statin or omega-3 usage. Radiomics models were trained on selected features and evaluated with 500-round threefold cross-validation for each drug/ROI combination. On the 1500 validation datasets, the radiomics model achieved average AUCs of 0.70, 0.74, 0.78, and 0.72 for omega-3/prostate, omega-3/peripheral, statin/prostate, and statin/peripheral, respectively. As the first study to analyze radiomics in relation to statin and omega-3 uses in prostate cancer patients, our study preliminarily established the existence of imaging-identifiable tissue-level changes in the prostate and illustrated the potential usefulness of radiomics for further exploring these medications’ effects and mechanisms in prostate cancer.