This study evaluated the potential of red pitaya pulp fermented with Lacticaseibacillus paracasei subsp. paracasei F-19 (F-19) as a base for probiotic products. Physicochemical parameters, sugar, betacyanin, and phenolic contents, and antioxidant activity were analyzed over 28 days at 4 °C and compared to a non-fermented pulp, and to a pulp fermented with Bifidobacterium animalis subsp. lactis BB-12 (BB-12). Volatile compounds were identified using HS-SPME/GC–MS. Probiotic viability during storage and survival through in vitro-simulated gastrointestinal tract (GIT) stress were assessed. Red pitaya pulp, rich in moisture (85.83 g/100 g), carbohydrates (11.65 g/100 g), and fibers (2.49 g/100 g), supported fermentation by both strains. F-19 and BB-12 lowered pH, with F-19 showing stronger acidification, and maintained high viability (8.85–8.90 log CFU/mL). Fermentation altered sugar profiles and produced unique volatile compounds, enhancing aroma and sensory attributes. F-19 generated 2-phenylethanol, a unique flavor compound, absent in BB-12. Phenolic content initially increased but antioxidant activity decreased during storage. Betacyanin remained stable for up to 14 days. Red pitaya improved F-19 viability through the simulated GIT, while BB-12 populations significantly decreased (p < 0.05). These results suggest red pitaya pulp is a promising plant-based matrix for F-19, offering protection during digestion and highlighting its potential as a functional food with enhanced bioactive compound bioavailability and sensory attributes.