The understanding of complex molecular representations is crucial for comprehending molecular scientific phenomena, but many students struggle with them. Therefore, we investigated the effectiveness of short written clues in dealing with molecular representations, specifically their impact on performance, self-efficacy, and stress reactions. A total of 136 secondary school students participated and engaged in tasks involving complex molecular representations in a prior knowledge test and a main test. Half of the students received clues, while the other half did not. The results showed that students who received clues performed significantly better on the test, highlighting their effectiveness for improving performance. However, the clues had no influence on self-efficacy, which remained moderate for both groups. Physiological stress responses (heart rate variability) indicated that students without clues experienced increased stress during the main test, whereas those with clues maintained lower stress levels like those in the prior knowledge test. Subjective stress levels decreased for both groups from the prior knowledge test to the main test, with students who received clues tending to report lower stress levels. In conclusion, short written clues were found to be effective in improving performance and reducing stress levels when dealing with complex molecular representations, although long-term interventions may be required to enhance self-efficacy.