Journal of Intelligent Systems and Internet of Things JISIoT 2690-6791 2769-786X 10.54216/JISIoT https://www.americaspg.com/journals/show/3882 2019 2019 Business Department, Al Ain University, Al Ain, UAE Marwa Marwa Computer Technology Engineering Department, Engineering Technologies College, Al-Esraa University Baghdad, 1008, Iraq Walid Alayash Biomedical Engineering Department, Engineering College, Al-Esraa University Baghdad, 10081, Iraq Inas salah Mahmoud Computer Technology Engineering Department, Engineering Technologies College, Al-Esraa University Baghdad, 1008, Iraq Marwa Hussien Moahmed Recent advancements in biomedical data analysis have significantly transformed clinical decision-making. However, the inherent complexity and heterogeneity of healthcare data continue to present major challenges. Traditional deep learning models, while powerful, often lack transparency, limiting their adoption in clinical settings due to their "black-box" nature. To address this critical gap, this study introduces a novel Explainable Deep Learning (XDL) framework that integrates high predictive accuracy with interpretability, enabling clinicians to trust and validate AI-driven insights. The proposed framework leverages advanced interpretability techniques—such as Grad-CAM for visual attribution and SHAP for feature importance analysis—to analyze multimodal biomedical data, including clinical imaging, genomic sequencing, and electronic health records. Experimental evaluations across three benchmark datasets demonstrated the model’s strong performance, achieving an accuracy of 91%, sensitivity of 95.4%, specificity of 98.6%, and an AUC of 99%, while maintaining an interpretability score of 92% as rated by domain experts. Compared to non-explainable models, the proposed approach showed a 12.3% increase in interpretability and a 5.8% improvement in accuracy. Importantly, attention map analysis revealed alignment with clinically relevant biomarkers in 93% of cases and uncovered previously overlooked prognostic patterns in 18% of patient cohorts. These findings underscore the model’s potential to enhance diagnostic precision and support more informed clinical decisions. Moreover, the algorithm reduced diagnostic time by 23% due to its provision of actionable insights. The hybrid approach—combining built-in attention mechanisms with external interpretability tools—ensures seamless integration into clinical workflows while supporting compliance with regulatory standards for transparency. 2025 2025 88 100 10.54216/JISIoT.170207 https://www.americaspg.com/articleinfo/18/show/3882