In the context of competition between businesses becoming more and more evident today, exploiting the intellectual capital of businesses to help businesses enhance their competitiveness is considered one of the priorities that businesses should carry out. To clarify the impact of intellectual capital on innovation in small and medium-sized enterprises in the Mekong Delta, the study conducted a survey of 253 enterprises, including 82 enterprises operating in the industrial sector, 91 enterprises operating in the agricultural sector, and 80 enterprises operating in the service sector. The author conducted research through two stages: qualitative research and quantitative research. Besides, the data analysis method chosen by the author is (1) EFA exploratory factor analysis; (2) confirmatory factor analysis CFA; (3) test the model using linear structural equation SEM. The results of estimating the linear structural model (SEM) show that the components "Human capital" and "Organizational capital" are more dominant than "Social capital" affects the innovation activities of businesses and has a positive impact. Innovation activities have a positive impact on business performance, of which the strongest and decisive impact is "process innovation", followed by "organizational innovation", the third is "marketing innovation" and the lowest is "product innovation".