This study reports the effectiveness of nanoscience activities in enhancing secondary school students’ understanding of two chemistry concepts: structure of atom and acid and bases. For the purpose of this study, quasi experiment was employed to 163 Grade 10 students from the Northern Region of Malaysia. Sample from the experimental group was exposed to a series of nanoscience activities lasted for 10 weeks. Students’ understanding on the two chemistry concepts was tested using Chemistry Achievement Test (CAT). The CAT consists of multiple-choice questions and open-ended questions. Data obtained from CAT was analysed using one-way ANCOVA to identify the effectiveness of nanoscience activity in enhancing students’ understanding of chemistry concepts. The findings show that there were statistically significant differences between experimental and control groups’ mean scores (F (1,160) = 167.82, p < 0.05 ηp2 = 0.512) with the experimental group students reporting higher mean. The ANCOVA result indicated experimental group students’ understanding of chemistry concepts significantly higher than the comparison group. The qualitative analysis of open-ended responses further supports findings obtained from the quantitative analysis. The study suggests that integrating nanoscience into the contemporary teaching of chemistry is relevant and appropriate.