This work presents a system for a simultaneous non-invasive estimate of the blood glucose level (BGL) and the systolic (SBP) and diastolic (DBP) blood pressure, using a photoplethysmograph (PPG) and machine learning techniques. The method is independent of the person whose values are being measured and does not need calibration over time or subjects. The architecture of the system consists of a photoplethysmograph sensor, an activity detection module, a signal processing module that extracts features from the PPG waveform, and a machine learning algorithm that estimates the SBP, DBP and BGL values. The idea that underlies the system is that there is functional relationship between the shape of the PPG waveform and the blood pressure and glucose levels. As described in this paper we tested this method on 410 individuals without performing any personalized calibration. The results were computed after cross validation. The machine learning techniques tested were: ridge linear regression, a multilayer perceptron neural network, support vector machines and random forests. The best results were obtained with the random forest technique. In the case of blood pressure, the resulting coefficients of determination for reference vs. prediction were R(SBP)(2)=0.91, R(DBP)(2)=0.89, and R(BGL)(2)=0.90. For the glucose estimation, distribution of the points on a Clarke error grid placed 87.7% of points in zone A, 10.3% in zone B, and 1.9% in zone D. Blood pressure values complied with the grade B protocol of the British Hypertension society. An effective system for estimate of blood glucose and blood pressure from a photoplethysmograph is presented. The main advantage of the system is that for clinical use it complies with the grade B protocol of the British Hypertension society for the blood pressure and only in 1.9% of the cases did not detect hypoglycemia or hyperglycemia. Copyright © 2011 Elsevier B.V. All rights reserved.