Background/Objectives: The prevalence of the commensal gut bacterium species, Phascolarctobacterium faecium, has been associated with normal weight in humans. Preclinical evidence suggests that the strain P. faecium DSM 32890 exerts beneficial effects on metabolic and immune function in diet-induced obesity. Herein, we aimed to evaluate the safety and tolerability of this strain in a preclinical study and a pilot interventional trial in humans. Methods: A repeated-dose oral toxicity study of 28 days was performed in Wistar rats (male and female), during which adverse signs and clinical outcomes were assessed, along with histological, hematologic, biochemical, and immune markers. Subsequently, a pilot human intervention trial was conducted, including 20 participants (11 overweight and 9 normal weight) who received P. faecium DSM 32890 daily for 15 days. Body composition, dietary intake, physical activity, clinical data, perceived health, gastrointestinal symptoms, and blood analyses were assessed to determine tolerability and identify potential adverse effects. Results: In rats, the administration of the bacterium did not cause behavioral, physiological, histologic, immune, or biochemical alterations. In humans, there was no evidence of adverse effects on general health, hematological and biochemical profiles, bowel habits, or gastrointestinal symptoms. Overweight participants experienced reductions in flatulence and nausea after the intervention. Conclusions: The consumption of P. faecium DSM 32890 did not raise safety concerns and was well tolerated in rats and humans. The findings represent a step forward in the path toward future, longer-term studies to explore the potential efficacy.