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Gastrointestinal (GI) diseases constitute a leading problem in the human digestive system. Consequently, several studies have explored automatic classification of GI diseases as a means of minimizing the burden on clinicians and improving patient outcomes, for both diagnostic and treatment purposes. The challenge in using deep learning-based (DL) approaches, specifically a convolutional neural network (CNN), is that spatial information is not fully utilized due to the inherent mechanism of CNNs. This paper proposes the application of spatial factors in improving classification performance. Specifically, we propose a deep CNN-based spatial attention mechanism for the classification of GI diseases, implemented with encoder–decoder layers. To overcome the data imbalance problem, we adapt data-augmentation techniques. A total of 12,147 multi-sited, multi-diseased GI images, drawn from publicly available and private sources, were used to validate the proposed approach. Furthermore, a five-fold cross-validation approach was adopted to minimize inconsistencies in intra- and inter-class variability and to ensure that results were robustly assessed. Our results, compared with other state-of-the-art models in terms of mean accuracy (ResNet50 = 90.28, GoogLeNet = 91.38, DenseNets = 91.60, and baseline = 92.84), demonstrated better outcomes (Precision = 92.8, Recall = 92.7, F1-score = 92.8, and Accuracy = 93.19). We also implemented t-distributed stochastic neighbor embedding (t–SNE) and confusion matrix analysis techniques for better visualization and performance validation. Overall, the results showed that the attention mechanism improved the automatic classification of multi-sited GI disease images. We validated clinical tests based on the proposed method by overcoming previous limitations, with the goal of improving automatic classification accuracy in future work.