Introduction Bipolar Disorder (BD) is a psychiatric disorder known as manic depressive illness that causes unusual shifts in mood, energy, and ability to think clearly. Any imbalance in the individual's neurotransmitters, inflammatory responses, and environmental factors are considered the main reasons for BD pathogenesis. This study aimed to investigate the relationship between serum Interleukin 1 β (IL-1β), Interleukin 6 (IL-6), Brain-derived neurotrophic factor (BDNF), and gut microbiome with BD. Material and Methods The differences in serum levels of IL-1β, IL-6, and BDNF were assessed in BD patients and control group by ELISA assay. Statistical analysis was performed using GraphPad Prism software to compare the significant differences (p<0.05) between BD patients and the control group. The V4 region of 16S rRNA gene sequencing was used to evaluate the gut microbial diversity. Results The result showed no significant change in the BDNF levels of BP patients compared to the control group (p=0.397). There was a significant difference in the IL-6 level between control healthy individuals and BP patients, in which the IL-1β and IL-6 concentrations were significantly higher than the control group at p=0.0001 and p=0.0214, respectively. In addition, BD patients displayed alterations in gut microbial diversity compared to the control group. Phylum Bacteroidetes and Firmicutes were the dominant bacterial communities in BD patients and healthy groups, respectively. Conclusion Our findings regarding the different levels of IL-1, IL-6, and alteration of the gut microbiome in the BD patients compared to the control group could add new evidence to the existing literature that gut dysbiosis in BD and also the inflammatory markers would be considered as the potential biomarkers for diagnosis and treatment outcome prediction of BD.