Background: Recent studies have investigated the potential of treatments that modify the gut microbiome, such as fecal microbiota transplantation (FMT) and probiotics, in individuals with psychiatric illnesses. The aim of this study was to investigate the safety, tolerability, and efficacy of a novel gut microbiome therapeutic, Microbial Ecosystem Therapuetic-2 (MET-2), in people with depression and anxiety. Methods: In this phase 1, open-label trial, twelve adults diagnosed with Major Depressive Disorder and/or Generalized Anxiety Disorder were recruited. Participants consumed orally once daily an encapsulated microbial therapeutic, containing 40 strains of bacteria purified and lab-grown from a single healthy donor stool, for 8 weeks. Participants were assessed biweekly using clinical scales and questionnaires in order to evaluate the safety, efficacy, and tolerability of the therapeutic. Results: The therapeutic was found to be generally safe and tolerable, with limited adverse events and side effects, and no serious adverse events. Of the twelve individuals included in this study, nine responded to treatment (50% improvement in MADRS and/or GAD-7 scores from baseline to week 8 visit). Over the course of 10 weeks MET-2 significantly decreased mean MADRS and GAD-7 scores, MADRS [F (5, 55) = 8.784, p<0.0001 and GAD-7 F (5,55) = 9.638, p<0.0001]. Conclusion: The findings of this study are the first to provide evidence for the role of microbial ecosystem therapy in treating depression and anxiety. However, a double-blind, randomized controlled trial with a larger sample size is needed for more conclusive results. Trial Registration: This study was registered with clinicaltrials.gov (NCT04052451) on 09/08/2019.