In France, little data are available on mental health and well-being in academia, and nothing has been published about PhD students. From studies abroad, we know that doing a PhD is a difficult experience resulting in high attrition rates with significant financial and human costs. Here we focused on PhD students in biology at university Lyon 1. A first study aimed at measuring the mental health and well-being of PhD students using several generalist and PhD-specific tools. Our results on 136 participants showed that a large fraction of the PhD students experience abnormal levels of stress, depression and anxiety, and their mean well-being score is significantly lower than that of a British reference sample. French PhD student well-being is specifically affected by career uncertainty, perceived lack of progress in the PhD and perceived lack of competence, which points towards possible cultural differences of experiencing a PhD in France and the UK. In a second study, we carried out a positive psychology intervention. Comparing the scores of the test and control groups showed a clear effect of the intervention on reducing anxiety. We discuss our results and the possible future steps to improve French PhD students’ well-being.