We were interested in this work to make a comparison between the protective effect of the ethanolic extract of Urtica urens L. (UU) and the effect of the bisphosphonate (BP) against osteoporosis induced in rats by intraperitoneal (IP) and oral (gavage) administration. The female rats were ovariectomized to cause osteoporosis. Several biological, histological, and histomorphometric analyses were used to study bone development. The results indicate that the EtOH extract of UU has a positive effect against osteoporosis for both routes of administration (IP and gavage). This effect could be attributed to the high richness of UU leaves in flavonoids, polyphenols, vitamins (vitamin D), and minerals (Ca and P). UU and BP have a histology score at 4 after 12 weeks of ovariectomy and for 60 days. Biological, histological, and histomorphometric studies have shown that UU and BP have significantly similar effects on the treatment of osteoporosis with both routes of administration. This plant could have a lower affinity than BP, possibly related to the dose. On the other hand, we concluded that IP administration is better than oral administration.