Early screening for diabetes can promptly identify potential early stage patients, possibly delaying complications and reducing mortality rates. This paper presents a novel technique for early diabetes screening and prediction, called the Attention-Enhanced Deep Neural Network (AEDNN). The proposed AEDNN model incorporates an Attention-based Feature Weighting Layer combined with deep neural network layers to achieve precise diabetes prediction. In this study, we utilized the Diabetes-NHANES dataset and the Pima Indians Diabetes dataset. To handle significant missing values and outliers, group median imputation was applied. Oversampling techniques were used to balance the diabetes and non-diabetes groups. The data were processed through an Attention-based Feature Weighting Layer for feature extraction, producing a feature matrix. This matrix was subjected to Hadamard product operations with the raw data to obtain weighted data, which were subsequently input into deep neural network layers for training. The parameters were fine-tuned and the L2 regularization and dropout layers were added to enhance the generalization performance of the model. The model’s reliability was thoroughly assessed through various metrics, including the accuracy, precision, recall, F1 score, mean squared error (MSE), and R2 score, as well as the ROC and AUC curves. The proposed model achieved a prediction accuracy of 98.4% in the Pima Indians Diabetes dataset. When the test dataset was expanded to the large-scale Diabetes-NHANES dataset, which contains 52,390 samples, the test precision of the model improved further to 99.82%, with an AUC of 0.9995. A comparative analysis was conducted using multiple models, including logistic regression with L1 regularization, support vector machine (SVM), random forest, K-nearest neighbors (KNNs), AdaBoost, XGBoost, and the latest semi-supervised XGBoost. The feature extraction method using attention mechanisms was compared with the classical feature selection methods, Lasso and Ridge. The experiments were performed on the same dataset, and the conclusion was that the Attention-based Ensemble Deep Neural Network (AEDNN) outperformed all the aforementioned methods. These results indicate that the model not only performs well on smaller datasets but also fully leverages its advantages on larger datasets, demonstrating strong generalization ability and robustness. The proposed model can effectively assist clinicians in the early screening of diabetes patients. This is particularly beneficial for the preliminary screening of high-risk individuals in large-scale, extensive healthcare datasets, followed by detailed examination and diagnosis. Compared to the existing methods, our AEDNN model showed an overall performance improvement of 1.75%.