Phylogenetic relationships of Scrophulariaceae s. l.（sensu lato）and the closely related groups were explored with 129 plastid genomes representing 107 genera. Plastome sequences were downloaded from the GenBank. Based on coding sequences (CDS), phylogenetic trees were reconstructed using maximum likelihood（ML）and Bayesian inference（BI）approaches. The ML and BI analyses shared the same topology and the main clades were consistently recovered with high support. Of the 129 total nodes, 123 were supported by ML bootstrap value ≥70%. The result were as follows：（1）Scrophulariaceae s. l. was confirmed as polyphyletic. Fifty-one species with representatives of 37 genera from the Scrophulariaceae s.l. were assigned to seven families. These were Orobanchaceae, Paulowniaceae, Wightiaceae, Mazaceae, Linderniaceae, Scrophulariaceae s. s.（sensu stricto）, and Plantaginaceae.（2）Scrophulariaceae s.s. was a monophyletic group. In addition to the recognition of eight genera（including Bontia, Calamphoreus, Diocirea, Eremophila, Glycocystis, Leucophyllum, Scrophularia and Verbascum）comprised primarily of former members of Scrophulariaceae s.l., Buddleja which was originally placed in Loganiaceae, and Myoporum, traditionally placed in the Myoporaceae had been demonstrated to belong to this clade.（3）The Lamiales was monophyletic. Fourteen well-supported monophyletic clades were obtained corresponding to each family (Wightiaceae and Pedaliaceae for which only one species had been contained were not included). The relationships among the families were well resolved. Oleaceae formed a well-supported clade that was distinct from core Lamiales. Within the core Lamiales, four clades (Gesneriaceae, Plantaginaceae, Scrophulariaceae, and Linderniaceae) diverged before the remaining families grouping in two sister clades. Within one clade, two moderately to highly supported subclades were recovered. Lentibulariaceae was resolved as sister group to Acanthaceae, and Pedaliaceae was sister to Verbenaceae + Bignoniaceae. The other clade contained six families, with Lamiaceae, Mazaceae, Wightiaceae + Phrymaceae, and Paulowniaceae successively sister to Orobanchaceae. The results of our analyses indicate that the traditional Scrophulariaceae are an unnatural assemblage of plants distributed throughout the phylogenentic tree of Lamiales. Phylogenomics analyses based on plastid organelle have shown good potential for phylogenetic inference in Scrophulariaceae, more taxonomic sampling are needed to enhance our understanding of phylogenetic relationships of Scrophulariaceae in future studies.