In 2002, the Netherlands introduced legislation that made euthanasia and assisted suicide (EAS) lawful. Under this law, patients may request EAS for either physical or mental health problems if very strict criteria are fulfilled. Even so, doctors are not required to take part. Because general practitioners (GPs) handle the vast majority of these requests, they play a key role in deciding whether to accept applications from both patient groups. While EAS for people with physical illnesses has become quite common across the country, granting it for mental health problems is still fairly unusual and stirs ongoing debate, even though such requests keep increasing. The current study examines Dutch GPs’ willingness to approve and carry out EAS requests for physical versus mental conditions, and contrasts the thinking processes that shape those decisions. Researchers employed a concurrent mixed-methods design combining a quantitative survey and qualitative interviews. A total of 103 GPs answered the survey, which collected details about their background, views on the topic, past involvement with EAS, and responses to six randomly assigned case descriptions. These cases changed according to the type of health issue (cancer compared with depression) and the form of assistance (euthanasia versus assisted suicide), so that willingness to approve requests could be measured. In addition, 13 GPs participated in semi-structured interviews that provided a closer look at their personal reasoning and practical experiences. GPs showed a much lower readiness to approve EAS requests linked to mental health conditions than to physical ones (OR = 0.02, 95% CI [0.009–0.04]). Those who described themselves as religious were less likely to grant any requests (OR = 0.31, 95% CI [0.11–0.85]), and they generally preferred euthanasia to assisted suicide (OR = 2.3, 95% CI [1.31–4.03]). The exact diagnosis and earlier contact with mental health requests did not produce any meaningful difference. Actual readiness to carry out the procedure stood at 95.1% for physical conditions but dropped to 45.6% for mental conditions. GPs who had already performed EAS for someone with a mental health condition were far less likely to limit their involvement to physical cases only (OR = 0.15, 95% CI [0.02–0.73]). The interviews made clear that mental health situations felt considerably more complicated. Doctors pointed to problems with compliance with legal due care rules, struggles to align with the patient’s wishes, moral conflicts, much longer assessment times, and lower confidence in their own judgment. In mental health cases, they tended to ask for extra opinions from psychiatric experts and referred the matter to the Expertise Center Euthanasia (ECE) more frequently. Dutch GPs are noticeably less willing to approve or carry out EAS requests that concern mental health conditions than those that concern physical health conditions. This gap seems to arise from obstacles in evaluating the required due care standards, uncertainty in clinical judgment, trouble connecting emotionally with the request, drawn-out procedures, and greater ethical difficulty. The outcomes underline the importance of implementing current guidelines more effectively in everyday GP work, while also providing specific training and better support for doctors. Useful forms of support would include quick access to psychiatric knowledge, SCEN consultations, and tight teamwork with the Expertise Center Euthanasia (ECE).