Oyu is an alias for Oichi who is based off her namesake, Oda Oichi. Oichi was Oda Nobunaga's younger sister and was forced to divorce her husband and be married to Azai Nagamasa to broker an alliance between the Oda and Azai clans. After the Azai betrayed the Oda and were subsequently defeated, Oichi was honorably returned to her brother where she was remarried to her first husband.

Kotaro's character is based off a renown ninja of the Hojo clan, Fuuma Kotaro, the leader a group of ninja from Sagami province. Unlike the Kotaro of the game who appeared to be a young novice ninja, Kotaro was supposedly a forty-year-old ninja leader when Onimusha 2: Samurai's Destiny takes place around 1573.
Although in all likelihood, as Kotaro was a name accepted by numerous heads of the Fuuma family, this Kotaro could have been intended as the son of the aforementioned man, especially considering his character arc's ending.

Magoichi's character is based off one of the warlords to have held the name Saiga Magoichi, namely the second, Suzuki Shigehide. Shigehide was the son of a warlord from Kii province, Suzuki Shigeoki, and he led arquebuse units in defense of the warrior monks of the Honganji.

Ekei's character is based off a combination of his namesake, Ankokuji Ekei and the monk-warrior, Hozoin Inei. Inei was a warrior monk and founder of the Hozoin style of spear fighting.
Ankokuji Ekei was the abbot of Ankoku Temple and served the Mori clans. Unlike his in-game caricature he was small-framed and had very little combat training; he was sometimes referred to as "Motonari's Little Monk" by his contemporaries.

Many of the characters in Onimusha are based off real people. Most obviously Oda Nobunaga, Toyotomi Hideyoshi, and Akechi Samanosuke (Hidemitsu) either return or are referenced from their actions in Onimusha: Warlords.
The main character, Yagyu Jubei, is based on the swordsman and small-time warlord Yagyu Muneyoshi, founder of the Yagyu Shinkage-ryu style of swordsmanship.

Jubei's likeness in the game is based off the late Japanese movie star, Matsuda Yusaku (1949-1989).
Matsuda's likeness was also used for Aokiji from One Piece.