Endoscopic procedures for diagnosing gastrointestinal tract findings depend on specialist experience and inter-observer variability. This variability can cause minor lesions to be missed and prevent early diagnosis. In this study, deep learning-based hybrid stacking ensemble modeling has been proposed for detecting and classifying gastrointestinal system findings, aiming at early diagnosis with high accuracy and sensitive measurements and saving workload to help the specialist and objectivity in endoscopic diagnosis. In the first level of the proposed bi-level stacking ensemble approach, predictions are obtained by applying 5-fold cross-validation to three new CNN models. A machine learning classifier selected at the second level is trained according to the obtained predictions, and the final classification result is reached. The performances of the stacking models were compared with the performances of the deep learning models, and McNemar’s statistical test was applied to support the results. According to the experimental results, stacking ensemble models performed with a significant difference with 98.42% ACC and 98.19% MCC in the KvasirV2 dataset and 98.53% ACC and 98.39% MCC in the HyperKvasir dataset. This study is the first to offer a new learning-oriented approach that efficiently evaluates CNN features and provides objective and reliable results with statistical testing compared to state-of-the-art studies on the subject. The proposed approach improves the performance of deep learning models and outperforms the state-of-the-art studies in the literature.