Glycated hemoglobin and blood oxygenation are the two most important factors for monitoring a patient’s average blood glucose and blood oxygen levels. Digital volume pulse acquisition is a convenient method, even for a person with no previous training or experience, can be utilized to estimate the two abovementioned physiological parameters. The physiological basis assumptions are utilized to develop two-finger models for estimating the percent glycated hemoglobin and blood oxygenation levels. The first model consists of a blood-vessel-only hypothesis, whereas the second model is based on a whole-finger model system. The two gray-box systems were validated on diabetic and nondiabetic patients. The mean absolute errors for the percent glycated hemoglobin (%HbA1c) and percent oxygen saturation (%SpO2) were 0.375 and 1.676 for the blood-vessel model and 0.271 and 1.395 for the whole-finger model, respectively. The repeatability analysis indicated that these models resulted in a mean percent coefficient of variation (%CV) of 2.08% and 1.74% for %HbA1c and 0.54% and 0.49% for %SpO2 in the respective models. Herein, both models exhibited similar performances (HbA1c estimation Pearson’s R values were 0.92 and 0.96, respectively), despite the model assumptions differing greatly. The bias values in the Bland–Altman analysis for both models were – 0.03 ± 0.458 and – 0.063 ± 0.326 for HbA1c estimation, and 0.178 ± 2.002 and – 0.246 ± 1.69 for SpO2 estimation, respectively. Both models have a very high potential for use in real-world scenarios. The whole-finger model with a lower standard deviation in bias and higher Pearson’s R value performs better in terms of higher precision and accuracy than the blood-vessel model.