MediaPipe Hand (MediaPipe) is an artificial intelligence (AI)-based pose estimation library. In this study, MediaPipe was combined with four machine learning (ML) models to estimate the rotation angle of the thumb. Videos of the right hands of 15 healthy volunteers were recorded and processed into 9000 images. The rotation angle of the thumb (defined as angle θ from the palmar plane, which is defined as 0°) was measured using an angle measuring device, expressed in a radian system. Angle θ was then estimated by the ML model by using parameters calculated from the hand coordinates detected by MediaPipe. The linear regression model showed a root mean square error (RMSE) of 12.23, a mean absolute error (MAE) of 9.9, and a correlation coefficient of 0.91. The ElasticNet model showed an RMSE of 12.23, an MAE of 9.95, and a correlation coefficient of 0.91; the support vector machine (SVM) model showed an RMSE of 4.7, an MAE of 2.5, and a correlation coefficient of 0.99. The LightGBM model achieved high values: an RMSE of 4.58, an MAE of 2.62, and a correlation coefficient of 0.99. Based on these findings, we concluded that the thumb rotation angle can be estimated with high accuracy by combining MediaPipe and ML.