Objective Postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) are the two main forms of functional dyspepsia (FD). Probiotics are a promising therapy for FD, but current data remains heterogeneous. This work aims to evaluate a probiotic combination of Lacticaseibacillus rhamnosus LR04 (DSM 16605), Lactiplantibacillus pentosus LPS01 (DSM 21980), Lactiplantibacillus plantarum LP01 (LMG P-21021), and Lactobacillus delbrueckii subsp. delbruekii LDD01 (DMS 22106), alone or together with other pharmacological therapies, for clinical improvement of symptoms associated with FD. Methods Patients with FD were enrolled and divided into two groups: PDS and EPS. Probiotic alone or combined with prokinetics, antacids, or proton-pump-inhibitors were administered for 30 days. A progressive-score scale was used to evaluate symptoms in all patients at the beginning of the trial and at 15 days after the end of treatment. Results A cohort of 2676 patients were enrolled (1 357 with PDS; 1 319 with EPS). All patients showed significant improvements in dyspeptic symptoms following treatment. In patients with PDS, probiotic alone resulted in the lowest prevalence of symptoms following treatment, while patients with EPS showed no clear between-treatment differences. Conclusions Dyspeptic symptoms were reduced following treatment in all patients.