The aim of this study was to assess cognitive performance and heart rate variability (HRV) following the ingestion of either a multi-vitamin-mineral preparation supplemented with 300 mg guarana (Ac); a caffeine supplement (C) or a placebo supplement (Pl). Fifty-six subjects took part in a randomized, double-blind crossover design, consisting of three experimental sessions ran on a different day. Cognitive performance was assessed using a go/no-go task and a simple reaction time (SRT) task. HRV was assessed in the time domain (RMSSD) and in the frequency domain (HF) and cognitive tasks were performed before ingestion, 15 min after ingestion and then every 15 min over the course of 3 h. Responses were faster (without change in accuracy) when the go/no-go task was performed between 30 and 90 min after ingestion of Ac (4.6% ± 0.8%, p < 0.05). No effect was observed on SRT task. A significant decrease in HRV was observed during the first hour under C and Pl, whereas HRV remained stable under Ac. The results suggest that the ingestion of a multi-vitamin-mineral with added guarana improves decision-making performance and is accompanied by a stable autonomic nervous system regulation during the first hour.