Probiotics can improve the intestinal environment by enhancing beneficial bacteria to potentially regulate lipid levels; however, the underlying mechanisms remain unclear. The aim of this study was to investigate the effect of Lactobacillus plantarum Q180 (LPQ180) on blood lipid levels and the intestinal microbiome environment from a clinical perspective. A double-blind, randomized, placebo-controlled study was conducted including 70 participants of both sexes, 20 years of age and older, with blood triacylglyceride (TG) levels below 200 mg/dL. Treatment with LPQ180 for 12 weeks significantly decreased LDL-cholesterol (p = 0.042) and apolipoprotein (Apo)B-100 (p = 0.003) levels, and decreased postprandial maximum concentrations (Cmax) and areas under the curve (AUC) of TG, chylomicron TG, ApoB-48, and ApoB-100. LPQ180 treatment significantly decreased total indole and phenol levels (p = 0.019). In addition, there was a negative correlation between baseline microbiota abundance and lipid marker change, which was negatively correlated with metabolites related to harmful bacteria. LPQ180 treatment may help prevent hypertriglyceridemia by improving fasting and postprandial blood lipid levels. In addition, LPQ180 effectively prevented the growth of harmful bacteria, particularly in subjects with higher baseline levels of harmful gut microbiota. Probiotics can improve the intestinal environment by enhancing beneficial bacteria to potentially regulate lipid levels; however, the underlying mechanisms remain unclear. The aim of this study was to investigate the effect of Lactobacillus plantarum Q180 (LPQ180) on blood lipid levels and the intestinal microbiome environment from a clinical perspective. A double-blind, randomized, placebo-controlled study was conducted including 70 participants of both sexes, 20 years of age and older, with blood triacylglyceride (TG) levels below 200 mg/dL. Treatment with LPQ180 for 12 weeks significantly decreased LDL-cholesterol (p = 0.042) and apolipoprotein (Apo)B-100 (p = 0.003) levels, and decreased postprandial maximum concentrations (Cmax) and areas under the curve (AUC) of TG, chylomicron TG, ApoB-48, and ApoB-100. LPQ180 treatment significantly decreased total indole and phenol levels (p = 0.019). In addition, there was a negative correlation between baseline microbiota abundance and lipid marker change, which was negatively correlated with metabolites related to harmful bacteria. LPQ180 treatment may help prevent hypertriglyceridemia by improving fasting and postprandial blood lipid levels. In addition, LPQ180 effectively prevented the growth of harmful bacteria, particularly in subjects with higher baseline levels of harmful gut microbiota.