The effect of a healthy low-carbohydrate diet (HLCD) and time-restricted eating (TRE), alone or in combination, on body weight and gut microbiome beyond caloric restriction remains unclear. In this 12-week two-by-two factorial randomized trial with a 28-week follow-up among 96 participants with overweight or obesity, isocaloric-restricted feeding yields significant weight loss, ranging from 2.57 to 4.11 kg across different groups. Beyond caloric restriction, HLCD and TRE lead to additional reduction in body mass index. HLCD results in additional fat mass loss while TRE yields more lean mass loss. Additionally, HLCD leads to decreased fecal branched-chain amino acids, and TRE tends to yield an increased abundance of probiotic species involved in synthesizing short-chain fatty acids. Moreover, the effect of HLCD on reducing fat mass is sustained during the post-intervention follow-up. Overall, HLCD and TRE are effective in weight management and yield profound gut microbiome and metabolome alteration beyond caloric restriction. This study was registered at ChiCTR.org.cn (ChiCTR2200056363).