Among them will be Charles Duncan, 40, and his 13-year-old daughter Emma who are taking part to raise awareness about a rare and life-threatening medical condition that affects Mr Duncan's eight-year-old son Charlie.
Charlie, from Glasgow, has already undergone 10 operations in the past 18 months.
The first sign anything was wrong came two Christmases ago when his mouth started bleeding heavily.
Initially, it was believed to be caused by a dental problem, but when symptoms became worse doctors discovered a large lesion inside his mouth.
Charlie was diagnosed with mandibular arteriovenous malformation (AVM) - caused by an abnormal connection between the body's arteries and veins. It more typically occurs in the brain and can mimic symptoms similar to a stroke.
Charlie's AVM is in his mouth and doctors know of only one other child in the UK affected this way.
Mr Duncan and Emma are fundraising for the Southern General and Royal Hospital for Sick Children at Yorkhill, where Charlie was due to undergo his 11th operation last night.
Mr Duncan said: "We are hoping to not only spread awareness about this rare condition, but raise money as a way to say thank you to the staff who have helped look after Charlie.
"The service we have received at both hospitals, from David Koppel of the Southern General Regional Maxillofacial Unit and all the doctors and nurses at Yorkhill, has been out of this world. Between us, Emma and I have managed to raise £1500 so far but are hoping to add to that."
The father-and-daughter team will tackle the half-mile distance in chilly waters. "We have been training hard, but know it will be tough," said Mr Duncan. "I have a few nerves: it's a deep, dark loch and completely different to swimming in a pool."
Fortunately, world-class advice was on hand as the whole family, including Charlie's mother Jacqueline, 40, met Commonwealth Games gold medallist swimmer Robbie Renwick for some last-minute tips.
Renwick, who held a masterclass in open-water swimming at Loch Lomond, described the Duncans and other fundraisers taking part in the event as "inspirational".
He said: "It was really great to meet them. I taught them a few bits and bobs that will hopefully help on Saturday. I know Charlie is going in for his operation and wish him all the best."
Renwick will be joined in tomorrow's elite race by German world champion Christian Reichert and Olympian Chad Ho from South Africa.
Two-time Commonwealth Games gold medallist Caitlin McClatchey and double world champion Keri-anne Payne will lead a world-class field in the women's event.
Former Olympic 400m runner turned television presenter, Iwan Thomas, will also be taking part.
l For more information, visit www.greatswim.org/scotland
l To help the Duncans in their fund-raising bid, visit www.justgiving.com/Emma-Duncan3