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The usefulness of antibiotics in dogs with acute diarrhea (AD) is controversial. It is also unclear what effect metronidazole has on potential enteropathogens such as <i>Clostridium perfringens</i> and <i>Escherichia coli</i>. Thus, the aim of this study was to evaluate the effect of metronidazole vs. a synbiotic on the clinical course and core intestinal bacteria of dogs with AD. Twenty-seven dogs with AD were enrolled in this prospective, randomized, blinded clinical trial and treated with either metronidazole (METg) or a synbiotic (SYNg; <i>E. faecium</i> DSM 10663; NCIMB 10415/4b170). The Canine Acute Diarrhea Severity (CADS) index was recorded daily for eleven days. Bacteria were quantified using qPCR. Data were analyzed using mixed models with repeated measures. A higher concentration of <i>E. coli</i> was observed in the METg group vs. the SYNg group on Day 6 (<i>p</i> < 0.0001) and Day 30 (<i>p</i> = 0.01). Metronidazole had no effect on <i>C. perfringens. C. hiranonis</i> was significantly lower in the METg group than in the SYNg group on Days 6 and 30 (<i>p</i> < 0.0001; <i>p</i> = 0.0015). No significant differences were observed in CADS index, fecal consistency, or defecation frequency between treatment groups (except for the CADS index on one single day). In conclusion, metronidazole negatively impacts the microbiome without affecting clinical outcomes. Thus, synbiotics might be a preferred treatment option for dogs with AD.