Rena Ryūgū, originally named Reina Ryūgū, was born in Hinamizawa before relocating to Ibaraki for her mother's career. There, her mother initiated an affair, announced pregnancy with her partner, and planned divorce. Rena opposed this, leading to estrangement. Post-divorce, she blamed herself and suffered mental deterioration, culminating in a violent attack on three male classmates with a baseball bat, permanently injuring one and shattering school windows. This resulted in psychiatric hospitalization, where she developed delusions of maggots infesting her blood and engaged in self-harm. She claimed Oyashiro-sama’s voice instructed her return to Hinamizawa for safety. After moving back with her father in April, she insisted on being called "Rena"—symbolically removing "i" to discard "icky" elements, though acknowledging it also removed "incredible" aspects.

In Hinamizawa, Rena displays a dual personality. Outwardly cheerful and caring, she walks to school with Keiichi Maebara and prepares meals for friends. She obsesses over objects or people deemed "cute," entering "Cute Mode" while exclaiming "Hauu~! I want to take it home~!" ("Omochikaerii~!"). This fixation drives her to collect discarded items at the village junkyard, where she maintains a secret base inside an old van. She frequently repeats phrases with "kana, kana?" ("I wonder, I wonder?"). However, she harbors intense aversion to lies, becoming hostile or violent when deceived or when Oyashiro-sama’s existence is questioned. During these outbursts, her eyes lose their light, and she wields a nata as her signature weapon.

Rena exhibits high perceptiveness, deducing complex situations from minor clues—such as inferring characters' whereabouts from household items—and accurately reconstructing crime scenes. She forms a close bond with Keiichi, with implied romantic feelings, and shows protectiveness toward younger club members like Satoko Hojo and Rika Furude. She feels guilt over not aiding Satoko’s brother, Satoshi, before his disappearance. Her belief in Oyashiro-sama’s curse stems from Hinamizawa Syndrome, causing paranoia and hallucinations resembling schizophrenia and delusional parasitosis. Symptoms include hearing an extra footstep, a woman apologizing, and sensing Oyashiro-sama watching at night.

Her actions diverge across story arcs. In Tsumihoroboshi-hen, she kills scam artists Rina Mamiya and Teppei Hōjō to protect her father, then takes schoolchildren hostage after reading Takano Miyo’s scrapbook, believing her friends conspired against her. Keiichi intervenes to prevent further violence. In Minagoroshi-hen, she intimidates village elders and child welfare workers, engaging in physical fights. In Onikakushi-hen, she confronts Keiichi with a hatchet after he accuses her of lying, chasing him while insisting Oyashiro-sama caused village disappearances. Later, she nurses him during illness, reflecting her duality of care and menace.

In later timelines, Rena attends Gogura University with Keiichi and Mion Sonozaki by 1988. As an adult, she wears a purple business suit, retains a similar hairstyle, and stands taller than in her youth. In the Rei arc (2019), she has a son named Kihiro. Her blood-stained beret serves as a symbolic distress signal in certain arcs.

Physically, Rena has short, uneven orange hair with longer front locks and spiky bangs, paired with lavender-blue eyes. Her standard outfit is a sailor-style school uniform with a yellow scarf, white socks, and dark shoes. Casually, she wears a white dress with a purple bow, white beret, black thigh-high socks, and brown boots. In special scenarios, she dons a yellow bikini with leaf-shaped bows or an Angel Mort waitress uniform featuring cat ears and a tail.