Pre-exercise caffeine and guarana-based multi-ingredient supplement (MS) consumption may be more effective for physical performance improvement than caffeine and guarana alone due to the synergistic effect of biologically active ingredients in multi-ingredient supplements. This study aimed to examine the acute effect of MS on the reactive agility and jump performance in recreational handball male players. A randomized, double-blind, crossover study involved twenty-four male handball players (body mass 74.6 ± 8.8 kg; body height 179 ± 7 cm; age 23.8 ± 1.4 years). Participants were tested under three conditions: placebo, caffeine + guarana (CAF + GUA), or MS ingestion 45 min before exercise tests. Participants performed a reactive agility test (Y-shaped test) and countermovement jump (CMJ). None of the supplements improved countermovement jump height (p = 0.06). The time needed to complete the agility test was significantly (p = 0.02) shorter in the MS condition than in the placebo. The differences in agility between PL vs. CAF + GUA and MS vs. CAF + GUA conditions were not statistically significant (p = 0.88 and p = 0.07, respectively). The results of this study indicate that the caffeine-based multi-ingredient performance was effective in improvement in reactive agility but not in jump height in recreational handball male players. A similar effect was not observed with CAF + GUA ingestion alone.