Blastocystis sp. has been considered as an opportunistic intestinal parasite particularly in immunocompromised patient. Recent findings of the predominance of Blastocystis subtypes infection in the clinical disease with its interaction with gut microbiota in the hosts will be discussed accordingly. A total of 57 eligible studies, published from 2010 to October 2020 from a broad search in electronic databases were accessed. The studies showed that bloating, abdominal pain and diarrhoea were among the common symptoms in Blastocystis sp. infection in the immunocompromised patients. However, asymptomatic and healthy individuals were also infected by the Blastocystis sp. with higher prevalence among healthy individuals. Specifically, Blastocystis sp. ST3 were most frequently discovered among immunocompromised patients (IBS, cancer, transplant, HIV/AIDS, dengue) followed by ST1 and ST2. Despite most studies suggesting that Blastocystis sp. promote a healthy gut, a few studies had suggested otherwise. Blastocystis sp. colonisation may modify the gut microbiota with the reduction of beneficial bacteria phyla such as Firmicutes and Bacteroides. Although there was a positive association between Blastocystis sp. subtypes and clinical diseases, more studies are needed. To understand the pathogenicity of Blastocystis sp., their interactions with the gut microbiota communities in humans are properly discussed.