Rhubarb (Rheum rhabarbarum L.) is a widely consumed vegetable valued for its vibrant red stalks and tart flavor. This study investigates the impact of hydroponic systems on rhubarb's growth, yield, and biochemical composition. Plants grown in hydroponic (volcanic slag and volcanic slag mixed with gravel medium) demonstrated a significant increase in both fresh and dry weight, with yields 2.6–6.0 times greater than those grown in traditional soil, particularly in June and July. Hydroponically grown rhubarb also produced 1.6–1.8 times more petioles per plant, each with 1.6 times the fresh weight and 1.1 times the dry weight of soil-grown petioles. In addition, hydroponic media enhanced the levels of plant extracts (1.2–3.2 times), total flavonoids (1.4–3.7 times), and total phenols (1.2–4.0 times) compared to soil-grown plants. DPPH antioxidant activity was also superior in hydroponically grown rhubarb, particularly in the mixture of volcanic slag and gravel medium, which exhibited the highest antioxidant capacity. According to FRAP analysis, soil-grown plants recovered more iron, followed by those in volcanic slag. Hydroponic plants grown in volcanic slag showed significantly higher concentrations of chlorogenic acid, rutin, quercetin, and ferulic acid compared to those grown in the mixture of volcanic slag and gravel. However, quercetin content was similar between soil and volcanic slag-grown plants. These findings suggest that hydroponic systems, especially those using the volcanic slag medium, hold promise for cultivating rhubarb enriched with health-promoting compounds.