Games like Little Sister
Games like Little Sister include Unpacking, Zup! S, Muse Dash, Slime Rancher 2, and your wife. We matched them by the tags players give Little Sister on Steam (Casual, Idler, 2D, Cute, and Relaxing): closest matches first, and among equally close ones the better-known games.

Unpacking
Shared: Casual · Cute · Relaxing

Zup! S
Shared: Casual · 2D · Indie

Muse Dash
Shared: Cute · Casual · Female Protagonist

Slime Rancher 2
Shared: Cute · Relaxing · Singleplayer

your wife
Shared: Casual · Cute · 2D

Keep on Mining!
Shared: Idler · Casual · Relaxing

Chill with You : Lo-Fi Story
Shared: Casual · Relaxing · Idler

Assemble with Care
Shared: Casual · Relaxing · Indie

Melvor Idle
Shared: Idler · Casual · 2D

Shelldiver
Shared: Casual · Idler · 2D

Cookie Clicker
Shared: Idler · Casual · Indie

Florence
Shared: Casual · Indie · Cute

Cat Goes Fishing
Shared: 2D · Cute · Casual

Screen Cat
Shared: Casual · Cute · Idler

A Game About Feeding A Black Hole
Shared: Casual · Relaxing · Idler

Carto
Shared: Cute · Indie · Relaxing

A Little to the Left
Shared: Relaxing · Casual · Cute

Your Mother
Shared: 2D · Female Protagonist · Cute

Tiny Pasture
Shared: Idler · Cute · Casual

When The Past Was Around
Shared: Cute · Relaxing · Female Protagonist

Is This Seat Taken?
Shared: Casual · Cute · Relaxing

A Short Hike
Shared: Relaxing · Cute · Casual

Zup!
Shared: Casual · 2D · Indie

Sticky Business
Shared: Casual · Relaxing · Cute