In obesity, to reduce visceral adipose tissue (VAT), caloric restriction is a valid strategy. Salivary amylase is an enzyme that cleaves large starch carbohydrates molecules and its production is modulated by the central nervous system. In addition, heart rate variability (HRV) is simply a measure of the variation in time between each heartbeat. This variation is controlled by the autonomic nervous system. In the light of this evidence, the aim of this study is to characterize the effect of a very low-calorie ketogenic diet (VLCKD) on the autonomic nervous system in obese patients. Twenty subjects affected by obesity were recruited before and after 8 weeks of VLCKD intervention to evaluate salivary amylase by the ELISA test and HRV analysis. These parameters significantly increased after dietary treatment, and positively correlate to each other. VLCKD exerts a positive effect on salivary amylase and HRV, ameliorating body composition and biochemical features. In brief, this dietary intervention improves the autonomic nervous system activity. This is the first study about the effects of VLCKD upon the autonomic nervous system, but further studies are needed to elucidate the mechanism undergone VLCKD effects.