Background: Despite abundant evidence demonstrating the benefits of continuous glucose monitoring (CGM) in diabetes management, a significant proportion of people using this technology still struggle to achieve glycemic targets. To address this challenge, we propose the Accu-Chek® SmartGuide Predict app, an innovative CGM digital companion that incorporates a suite of advanced glucose predictive functionalities aiming to inform users earlier about acute glycemic situations. Methods: The app’s functionalities, powered by three machine learning models, include a two-hour glucose forecast, a 30-minute low glucose detection, and a nighttime low glucose prediction for bedtime interventions. Evaluation of the models’ performance included three data sets, comprising subjects with T1D on MDI (n = 21), subjects with type 2 diabetes (T2D) on MDI (n = 59), and subjects with T1D on insulin pump therapy (n = 226). Results: On an aggregated data set, the two-hour glucose prediction model, at a forecasting horizon of 30, 45, 60, and 120 minutes, achieved a percentage of data points in zones A and B of Consensus Error Grid of: 99.8%, 99.3%, 98.7%, and 96.3%, respectively. The 30-minute low glucose prediction model achieved an accuracy, sensitivity, specificity, mean lead time, and area under the receiver operating characteristic curve (ROC AUC) of: 98.9%, 95.2%, 98.9%, 16.2 minutes, and 0.958, respectively. The nighttime low glucose prediction model achieved an accuracy, sensitivity, specificity, and ROC AUC of: 86.5%, 55.3%, 91.6%, and 0.859, respectively. Conclusions: The consistency of the performance of the three predictive models when evaluated on different cohorts of subjects with T1D and T2D on different insulin therapies, including real-world data, offers reassurance for real-world efficacy.