Cutaneous leishmaniasis (CL) remains a significant global public health disease, with the critical distinction and exact detection between responsive and unresponsive cases dictating treatment strategies and patient outcomes. However, image-based methods for differentiating these groups are unexplored. This study addresses this gap by developing a deep learning (DL) model utilizing transfer learning to automatically identify responses in CL lesions. A dataset of 102 lesion images (51 per class; equally distributed across train, test, and validation sets) is employed. The DenseNet161, VGG16, and ResNet18 networks, pretrained on a massive image dataset, are fine-tuned for our specific task. The models achieved an accuracy of 76.47%, 73.53%, and 55.88% on the test data, respectively, with a sensitivity of 80%, 75%, and 100% and specificity of 73.68%, 72.22%, and 53.12%, individually. Transfer learning successfully addressed the limited sample size challenge, demonstrating the models’ potential for real-world application. This work underscores the significance of automated response detection in CL, paving the way for treatment and improved patient outcomes. While acknowledging limitations like the sample size, the need for collaborative efforts is emphasized to expand datasets and further refine the model. This approach stands as a beacon of hope in the contest against CL, illuminating the path toward a future where data-driven diagnostics guide effective treatment and alleviate the suffering of countless patients. Moreover, the study could be a turning point in eliminating this important global public health and widespread disease.