Background: The amount of available textual health data such as scientific and biomedical literature is constantly growing and becoming more and more challenging for health professionals to properly summarize those data and practice evidence-based clinical decision making. Moreover, the exploration of unstructured health text data is challenging for professionals without computer science knowledge due to limited time, resources, and skills. Current tools to explore text data lack ease of use, require high computational efforts, and incorporate domain knowledge and focus on topics of interest with difficulty. Objective: We developed a methodology able to explore and target topics of interest via an interactive user interface for health professionals with limited computer science knowledge. We aim to reach near state-of-the-art performance while reducing memory consumption, increasing scalability, and minimizing user interaction effort to improve the clinical decision-making process. The performance was evaluated on diabetes-related abstracts from PubMed. Methods: The methodology consists of 4 parts: (1) a novel interpretable hierarchical clustering of documents where each node is defined by headwords (words that best represent the documents in the node), (2) an efficient classification system to target topics, (3) minimized user interaction effort through active learning, and (4) a visual user interface. We evaluated our approach on 50,911 diabetes-related abstracts providing a hierarchical Medical Subject Headings (MeSH) structure, a unique identifier for a topic. Hierarchical clustering performance was compared against the implementation in the machine learning library scikit-learn. On a subset of 2000 randomly chosen diabetes abstracts, our active learning strategy was compared against 3 other strategies: random selection of training instances, uncertainty sampling that chooses instances about which the model is most uncertain, and an expected gradient length strategy based on convolutional neural networks (CNNs). Results: For the hierarchical clustering performance, we achieved an F1 score of 0.73 compared to 0.76 achieved by scikit-learn. Concerning active learning performance, after 200 chosen training samples based on these strategies, the weighted F1 score of all MeSH codes resulted in a satisfying 0.62 F1 score using our approach, 0.61 using the uncertainty strategy, 0.63 using the CNN, and 0.45 using the random strategy. Moreover, our methodology showed a constant low memory use with increased number of documents. Conclusions: We proposed an easy-to-use tool for health professionals with limited computer science knowledge who combine their domain knowledge with topic exploration and target specific topics of interest while improving transparency. Furthermore, our approach is memory efficient and highly parallelizable, making it interesting for large Big Data sets. This approach can be used by health professionals to gain deep insights into biomedical literature to ultimately improve the evidence-based clinical decision making process.