Sulfites are the most widely used additives in oenology to prevent oxidation and microbial spoilage. However, concerns about their potential adverse health effects have increased demand for low-sulfite wines. Strategies are required to ensure microbiological stability while preserving wine quality. This study evaluated strategies to reduce or replace added sulfites with chitosan and low doses of lysozyme in Tannat winemaking. It measured their effects on microbial diversity, physicochemical parameters, and sensory attributes. Treatments were vinified in triplicate: reduced sulfites (RS: 30 mg/L), chitosan (C: 100 mg/L), reduced sulfites with chitosan (RS+C: 30 mg/L + 100 mg/L), reduced sulfites with lysozyme (RS+L: 30 mg/L + 5 mg/L), and traditional winemaking (TW: 125 mg/L sulfites). Sulfur dioxide lowered lactic acid bacteria counts, whereas chitosan and lysozyme treatments maintained higher populations. Metagenomic analyses showed that sulfur dioxide reduced bacterial diversity, whereas chitosan promoted a more complex microbiota. Lysozyme selectively reduced lactic acid bacteria, mainly affecting Oenococcus spp. Lower sulfite levels decreased phenolic concentrations, possibly due to reduced protection against oxidation, leading to color differences among treatments. The results indicate that strategies to reduce or replace sulfites influence microbial dynamics, acidity, phenolic structure, and color, highlighting the importance of careful process management to maintain wine quality.