The histological grade of oral squamous cell carcinoma affects the prognosis. In the present study, we performed a radiomics analysis to extract features from F-FDG PET image data, created machine learning models from the features, and verified the accuracy of the prediction of the histological grade of oral squamous cell carcinoma. The subjects were 191 patients in whom an F-FDG-PET examination was performed preoperatively and a histopathological grade was confirmed after surgery, and their tumor sizes were sufficient for a radiomics analysis. These patients were split in a 70%/30% ratio for use as training data and testing data, respectively. We extracted 2993 radiomics features from the PET images of each patient. Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), Naïve Bayes (NB), and K-Nearest Neighbor (KNN) machine learning models were created. The areas under the curve obtained from receiver operating characteristic curves for the prediction of the histological grade of oral squamous cell carcinoma were 0.72, 0.71, 0.84, 0.74, and 0.73 for LR, SVM, RF, NB, and KNN, respectively. We confirmed that a PET radiomics analysis is useful for the preoperative prediction of the histological grade of oral squamous cell carcinoma.