Objectives:To investigate the effect of Mediterranean diet (MedDiet) or mindfulness-based stress reduction (MBSR) in high-risk pregnancies on placental histopathological lesions. Methods: In a randomized clinical trial with parallel-group conducted at a University Hospital in Barcelona, Spain (2017-2020, 1221 pregnant women at high-risk for SGA were randomly allocated at 19-23 weeks of gestation into three groups: a MedDiet intervention, a MBSR program or non-intervention. Participants in the MedDiet group (n = 407) received monthly individual and group educational sessions, and free provision of extra-virgin olive oil and walnuts. Women in the MBSR group (n = 407) underwent an 8-week MBSR program adapted for pregnancy. While the primary outcome was the prevalence of SGA, placental histopathological lesions were considered as a secondary outcome, classified into vascular (maternal/fetal), immune-inflammatory and other lesions according to according to the 2014 Amsterdam Placental Workshop Group Consensus Statement. Results: Among 1182 participants considered for the intention-to-treat-analysis, 741 placentas were collected and studied (n = 257 non-intervention, n = 252 MedDiet, n = 253 MBSR). No differences were observed between the study groups in placental weight, placental dimensions, fetoplacental ratio or any of the placental lesions' categories. Likewise, no differences were detected between pregnancies with an SGA newborn from the three study groups (n = 59 non-intervention, n = 39 MedDiet, n = 37 MBSR). However, in pregnancies complicated by pre-eclampsia (n = 25 non-intervention, n = 17 MedDiet, n = 14 MBSR), we observed a tendency towards less maternal vascular lesions in MedDiet (35.3%, p = 0.19) and MBSR (21.4%, p = 0.05) compared to non-intervention (56%). Conclusions: Structured interventions during pregnancy based onMedDiet or MBSR may reduce maternal vascular placental lesions in pregnancies that develop pre-eclampsia. These results must be considered with caution since the trial was not designed for this specific outcome.